560 results
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2. The tissue distribution of NK-9 positive lymphoid cells including NK and AK cells and their precursors.
- Author
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Nieminen P
- Subjects
- Antibodies, Monoclonal, Collodion, Electrophoresis, Polyacrylamide Gel, Histocytochemistry, Humans, Lymph Nodes cytology, Lymphoid Tissue immunology, Palatine Tonsil cytology, Paper, Spleen cytology, Thymus Gland cytology, Tissue Distribution, Antigen-Presenting Cells immunology, Antigens, Surface immunology, Killer Cells, Natural immunology, Lymphoid Tissue cytology
- Abstract
The distribution of NK-9 antigen presenting cells in human lymphoid tissues including spleen, tonsil, lymph node, and thymus was studied. The staining were done on formalin-fixed, histological sections. In peripheral blood NK-9 antigens are expressed on allospecific (CTL) and nonspecific (NK and AK) cytotoxic lymphocytes. In lymphoid tissues, the distribution of NK-9 positive cells was definitely different from "normal" T cell distribution, measured by pan T monoclonal markers. In tonsils and lymph nodes NK-9 positive cells were mainly located in and around germinal centers. However, only a proportion of these areas were NK-9 positive. In spleen NK-9 positive cells were located mainly in periarteriolar lymphocyte sheats and in germinal centers. Thymuses were practically NK-9 negative. These results support the earlier suggestions that cytotoxic cells take part in the immunoregulation in lymphoid tissues.
- Published
- 1986
- Full Text
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3. Virion-surface display of a chimeric immunoglobulin Fc domain facilitating uptake by antigen-presenting cells.
- Author
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Seki S, Parbie PK, Yamamoto H, and Matano T
- Subjects
- Animals, Mice, Macrophages metabolism, Macrophages immunology, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Recombinant Fusion Proteins immunology, Simian Immunodeficiency Virus immunology, Simian Immunodeficiency Virus genetics, Hemagglutinin Glycoproteins, Influenza Virus immunology, Hemagglutinin Glycoproteins, Influenza Virus genetics, Hemagglutinin Glycoproteins, Influenza Virus metabolism, Cell Line, Leukemia Virus, Murine genetics, Phagocytosis, Humans, Immunoglobulin Fc Fragments genetics, Immunoglobulin Fc Fragments metabolism, Immunoglobulin Fc Fragments immunology, Antigen-Presenting Cells immunology, Antigen-Presenting Cells metabolism, Virion metabolism, Virion genetics, Dendritic Cells immunology, Dendritic Cells metabolism
- Abstract
Antigen-presenting cells (APCs) play an important role in virus infection control by bridging innate and adaptive immune responses. Macrophages and dendritic cells (DCs) possess various surface receptors to recognize/internalize antigens, and antibody binding can enhance pathogen-opsonizing uptake by these APCs via interaction of antibody fragment crystallizable (Fc) domains with Fc receptors, evoking profound pathogen control in certain settings. Here, we examined phagocytosis-enhancing potential of Fc domains directly oriented on a retroviral virion/virus-like particle (VLP) surface. We generated an expression vector coding a murine Fc fragment fused to the transmembrane region (TM) of a retroviral envelope protein, deriving expression of the Fc-TM fusion protein on the transfected cell surface and production of virions incorporating the chimeric Fc upon co-transfection. Incubation of Fc-displaying simian immunodeficiency virus (SIV) with murine J774 macrophages and bone marrow-derived DCs derived Fc receptor-dependent enhanced uptake, being visualized by imaging cytometry. Alternative preparation of a murine leukemia virus (MLV) backbone-based Fc-displaying VLP loading an influenza virus hemagglutinin (HA) antigen resulted in enhanced HA internalization by macrophages, stating antigen compatibility of the design. Results show that the Fc-TM fusion molecule can be displayed on certain viruses/VLPs and may be utilized as a molecular adjuvant to facilitate APC antigen uptake., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
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4. Nanobody-liposomes as novel cancer vaccine platform to efficiently stimulate T cell immunity.
- Author
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Bouma RG, Nijen Twilhaar MK, Brink HJ, Affandi AJ, Mesquita BS, Olesek K, van Dommelen JMA, Heukers R, de Haas AM, Kalay H, Ambrosini M, Metselaar JM, van Rooijen A, Storm G, Oliveira S, van Kooyk Y, and den Haan JMM
- Subjects
- Animals, Humans, Mice, Female, Antigens, Neoplasm immunology, Antigens, Neoplasm administration & dosage, Lymphocyte Activation drug effects, Liposomes, Cancer Vaccines administration & dosage, Cancer Vaccines immunology, Single-Domain Antibodies immunology, Single-Domain Antibodies administration & dosage, T-Lymphocytes immunology, Mice, Inbred C57BL, Antigen-Presenting Cells immunology
- Abstract
Cancer vaccines can be utilized in combination with checkpoint inhibitors to optimally stimulate the anti-tumor immune response. Uptake of vaccine antigen by antigen presenting cells (APCs) is a prerequisite for T cell priming, but often relies on non-specific mechanisms. Here, we have developed a novel vaccination strategy consisting of cancer antigen-containing liposomes conjugated with CD169- or DC-SIGN-specific nanobodies (single domain antibodies) to achieve specific uptake by APCs. Our studies demonstrate efficient nanobody liposome uptake by human and murine CD169
+ and DC-SIGN+ APCs in vitro and in vivo when compared to control liposomes or liposomes with natural ligands for CD169 and DC-SIGN. Uptake of CD169 nanobody liposomes resulted in increased T cell activation by human APCs and stimulated naive T cell priming in mouse models. In conclusion, while nanobody liposomes have previously been utilized to direct drugs to tumors, here we show that nanobody liposomes can be applied as vaccination strategy that can be extended to other receptors on APCs in order to elicit a potent immune response against tumor antigens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
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5. Engineering antigen-presenting cells for immunotherapy of autoimmunity.
- Author
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Smith CT, Wang Z, and Lewis JS
- Subjects
- Humans, Animals, Antigen-Presenting Cells immunology, Autoimmune Diseases immunology, Autoimmune Diseases therapy, Immunotherapy methods, Autoimmunity immunology
- Abstract
Autoimmune diseases are burdensome conditions that affect a significant fraction of the global population. The hallmark of autoimmune disease is a host's immune system being licensed to attack its tissues based on specific antigens. There are no cures for autoimmune diseases. The current clinical standard for treating autoimmune diseases is the administration of immunosuppressants, which weaken the immune system and reduce auto-inflammatory responses. However, people living with autoimmune diseases are subject to toxicity, fail to mount a sufficient immune response to protect against pathogens, and are more likely to develop infections. Therefore, there is a concerted effort to develop more effective means of targeting immunomodulatory therapies to antigen-presenting cells, which are involved in modulating the immune responses to specific antigens. In this review, we highlight approaches that are currently in development to target antigen-presenting cells and improve therapeutic outcomes in autoimmune diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
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6. Ligand Recognition by the Macrophage Galactose-Type C-Type Lectin: Self or Non-Self?-A Way to Trick the Host's Immune System.
- Author
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Szczykutowicz J
- Subjects
- Male, Humans, Ligands, Macrophages metabolism, Lectins, C-Type metabolism, Galactose, Antigen-Presenting Cells metabolism
- Abstract
The cells and numerous macromolecules of living organisms carry an array of simple and complex carbohydrates on their surface, which may be recognized by many types of proteins, including lectins. Human macrophage galactose-type lectin (MGL, also known as hMGL/CLEC10A/CD301) is a C-type lectin receptor expressed on professional antigen-presenting cells (APCs) specific to glycans containing terminal GalNAc residue, such as Tn antigen or LacdiNAc but also sialylated Tn antigens. Macrophage galactose-type lectin (MGL) exhibits immunosuppressive properties, thus facilitating the maintenance of immune homeostasis. Hence, MGL is exploited by tumors and some pathogens to trick the host immune system and induce an immunosuppressive environment to escape immune control. The aims of this article are to discuss the immunological outcomes of human MGL ligand recognition, provide insights into the molecular aspects of these interactions, and review the MGL ligands discovered so far. Lastly, based on the human fetoembryonic defense system (Hu-FEDS) hypothesis, this paper raises the question as to whether MGL-mediated interactions may be relevant in the development of maternal tolerance toward male gametes and the fetus.
- Published
- 2023
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7. Editorial: Processing, presentation, and recognition of T cell determinants: From molecular insights to clinical applications.
- Author
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James EA
- Subjects
- Epitopes, T-Lymphocytes, Antigen-Presenting Cells
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
- Published
- 2023
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8. Preparation of Bead-supported Lipid Bilayers to Study the Particulate Output of T Cell Immune Synapses.
- Author
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Céspedes PF and Dustin ML
- Subjects
- Lymphocyte Activation, Synapses, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Helper-Inducer, Antigen-Presenting Cells, Lipid Bilayers metabolism
- Abstract
Antigen-presenting cells (APCs) present three activating signals to T cells engaged in physical contact: 1) antigen, 2) costimulation/corepression, and 3) soluble cytokines. T cells release two kinds of effector particles in response to activation: trans-synaptic vesicles (tSVs) and supramolecular attack particles, which transfer intercellular messengers and mediate cytotoxicity, respectively. These entities are quickly internalized by APCs engaged in physical contact with T cells, making their characterization daunting. This paper presents the protocol to fabricate and use Bead-Supported Lipid Bilayers (BSLBs) as antigen-presenting cell (APC) mimetics to capture and analyze these trans-synaptic particles. Also described are the protocols for the absolute measurements of protein densities on cell surfaces, the reconstitution of BSLBs with such physiological levels, and the flow cytometry procedure for tracking synaptic particle release by T cells. This protocol can be adapted to study the effects of individual proteins, complex ligand mixtures, pathogen virulence determinants, and drugs on the effector output of T cells, including helper T cells, cytotoxic T lymphocytes, regulatory T cells, and chimeric antigen receptor-expressing T cells (CART).
- Published
- 2022
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9. Astragalus-mediated stimulation on antigen-presenting cells could result in higher IL-21 production from CXCR5 + Tfh-like cells and better IL-21-mediated effector functions.
- Author
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Dong Q, Pu J, Du T, Xu S, Liu W, Liu L, Wang Z, and Cai C
- Subjects
- Adult, Astragalus propinquus immunology, Carcinoma, Renal Cell immunology, Drugs, Chinese Herbal, Female, Gene Expression Regulation, Neoplastic, Humans, Immunity, Humoral, Kidney Neoplasms immunology, Male, Medicine, Chinese Traditional, Middle Aged, Antigen-Presenting Cells immunology, CD8-Positive T-Lymphocytes immunology, Carcinoma, Renal Cell therapy, Germinal Center immunology, Interleukins metabolism, Kidney Neoplasms therapy, Receptors, CXCR5 metabolism, T-Lymphocytes, Helper-Inducer immunology
- Abstract
T cells in renal cell carcinoma (RCC) patients display multiple features of impairment and exhaustion. Here, we hypothesize that Astragalus membranaceus, a herbal medicine commonly used to accompany chemotherapy, might have adjuvating effects on T cells from RCC patients. To investigate this, circulating T cells from healthy individuals and RCC patients were cocultured ex vivo with aqueous extract from Astragalus. Functional characteristics of T cells in the absence and presence of Astragalus extract were then compared. We first identified a downregulation of IL-21 expression in RCC patients in association with a functional dysregulation of CXCR5
+ Tfh-like cells. Astragalus extract could significantly increase IL-21 expression in a dose-dependent manner. This Astragalus-mediated effect depended on the presence of antigen-presenting cells (APCs), as purified CXCR5+ Tfh-like cells presented little IL-21 upregulation following Astragalus stimulation. APCs primed by Astragalus extract also promoted IL-21 expression from Tfh-like cells. Interestingly, Astragalus-stimulated Tfh-like cells presented enhanced helper function and resulted in higher humoral responses and better CD8 T cell survival. This effect was dependent on the presence of IL-21. Overall, these data indicated that Astragalus could enhance IL-21 production and effector function from CXCR5+ Tfh-like cells in a manner that depended on the presence of APCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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10. Risk-period-cohort approach for averting identification problems in longitudinal models.
- Author
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Gunzler, Douglas D., Perzynski, Adam T., Dawson, Neal V., Kauffman, Kelley, Liu, Jintao, and Dalton, Jarrod E.
- Subjects
AGE ,LONGITUDINAL method ,GERONTOLOGY ,CYTOLOGY ,MONTE Carlo method - Abstract
In epidemiology, gerontology, human development and the social sciences, age-period-cohort (APC) models are used to study the variability in trajectories of change over time. A well-known issue exists in simultaneously identifying age, period and birth cohort effects, namely that the three characteristics comprise a perfectly collinear system. That is, since age = period−cohort, only two of these effects are estimable at a time. In this paper, we introduce an alternative framework for considering effects relating to age, period and birth cohort. In particular, instead of directly modeling age in the presence of period and cohort effects, we propose a risk modeling approach to characterize age-related risk (i.e., a hybrid of multiple biological and sociological influences to evaluate phenomena associated with growing older). The properties of this approach, termed risk-period-cohort (RPC), are described in this paper and studied by simulations. We show that, except for pathological circumstances where risk is uniquely determined by age, using such risk indices obviates the problem of collinearity. We also show that the size of the chronological age effect in the risk prediction model associates with the correlation between a risk index and chronological age and that the RPC approach can satisfactorily recover cohort and period effects in most cases. We illustrate the advantages of RPC compared to traditional APC analysis on 27496 individuals from NHANES survey data (2005–2016) to study the longitudinal variability in depression screening over time. Our RPC method has broad implications for examining processes of change over time in longitudinal studies. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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11. Genetic polymorphisms of proteasome subunit genes of the MHC-I antigen-presenting system are associated with cervical cancer in a Chinese Han population.
- Author
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Li C, Dai S, Yan Z, Zhang X, Liu S, Wang X, Wang J, Shi L, and Yao Y
- Subjects
- Adult, Case-Control Studies, Female, Gene Frequency genetics, Genotype, Humans, Middle Aged, Uterine Cervical Dysplasia genetics, Antigen-Presenting Cells immunology, Asian People genetics, Genetic Predisposition to Disease genetics, Histocompatibility Antigens Class I genetics, Polymorphism, Single Nucleotide genetics, Proteasome Endopeptidase Complex genetics, Uterine Cervical Neoplasms genetics
- Abstract
Proteasome subunit beta types 8 and 9 (PSMB8, PSMB9) play critical roles in the human leukocyte antigen class I (HLA I)-presenting system. Studies have suggested that polymorphisms in the PSMB8 and PSMB9 genes may influence the immune functions of PSMB8 and PSMB9, and thus be associated with various human cancers. We investigated associations involving single nucleotide polymorphisms (SNPs) rs2071543 in PSMB8, rs1351383, rs17587 and rs2127675 in PSMB9 and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer in a Chinese Han population. A total of 543 patients with CIN, 1008 patients with cervical cancer, and 1120 healthy individuals were enrolled. Agena MassArray was used for SNP genotyping of PSMB8 and PSMB9. Associations involving these SNPs and risk of CIN and cervical cancer were analysed. Our results showed that the PSMB8 T/T and T/G genotypes of rs2071543 may be associated with a higher risk of CIN (P = 0.011, OR = 1.35,95% CI: 1.07-1.70) and cervical cancer (P = 0.006, OR = 1.31, 95% CI: 1.08-1.59). For rs17587, the A allele (P = 0.001, OR = 1.303, 95% CI: 1.115-1.522), and the A/A and A/G genotypes (P = 0.001, OR = 1.36, 95% CI: 1.13-1.63) may be risk factors for cervical cancer. These results indicated that PSMB8 rs2071543 might influence susceptibility to CIN and cervical cancer, and PSMB9 rs17587 might influence cervical cancer susceptibility in a Chinese Han population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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12. α7 nAChRs expressed on antigen presenting cells are insensitive to the conventional antagonists α-bungarotoxin and methyllycaconitine.
- Author
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Mashimo M, Takeshima S, Okuyama H, Matsurida A, Murase M, Ono S, Kawashima K, and Fujii T
- Subjects
- Aconitine pharmacology, Animals, Antigen Presentation drug effects, Benzylidene Compounds pharmacology, Calcium Signaling drug effects, Cell Differentiation drug effects, Cells, Cultured, Cytokines metabolism, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Transgenic, Pyridines pharmacology, alpha7 Nicotinic Acetylcholine Receptor genetics, Aconitine analogs & derivatives, Antigen-Presenting Cells immunology, Bungarotoxins pharmacology, CD4-Positive T-Lymphocytes immunology, T-Lymphocytes, Regulatory immunology, alpha7 Nicotinic Acetylcholine Receptor metabolism
- Abstract
Expression of α7 nicotinic acetylcholine receptors (nAChRs) on antigen presenting cells (APCs), such as macrophages and dendritic cells, is now well established. We have shown that GTS-21, a selective α7 nAChR agonist, downregulates APC-dependent CD4
+ T cell differentiation into regulatory T cells (Tregs) and effector Th1, Th2 and Th17 cells by inhibiting antigen processing, thereby interfering with antigen presentation. α7 nAChRs on Jurkat human leukemic T cells require functional T cell receptors (TCRs)/CD3 and leukocyte-specific tyrosine kinase to mediate nicotine-induced Ca2+ -signaling via Ca2+ release from intracellular stores, and are insensitive to two conventional α7 nAChR antagonists, α-bungarotoxin (α-BTX) and methyllycaconitine (MLA). We investigated the effects of GTS-21, α-BTX and MLA on ovalbumin (OVA)-induced Th cytokine release from spleen cells isolated from OVA-specific TCR transgenic DO11.10 mice. We found that: (1) GTS-21 dose-dependently suppresses OVA-induced IFN-γ, IL-4 and IL-17 release, but neither α-BTX nor MLA alone affected the OVA-induced cytokine release. (2) Neither α-BTX nor MLA abolished the suppressive effects of GTS-21 on IFN-γ and IL-17 release from OVA-activated DO11.10 spleen cells. (3) GTS-21 significantly suppressed OVA-induced APC-dependent CD4+ T cell differentiation into Tregs. Neither MLA nor mecamylamine, a non-specific nAChR antagonist, abolished the suppressive effect of GTS-21 on Treg differentiation. These results suggest that α7 nAChRs on APCs involved in cytokine synthesis and T cell differentiation are insensitive to the conventional α7 nAChR antagonists, α-BTX and MLA, and that α7 nAChRs on APCs differ pharmacologically from those in neurons., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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13. The epigenetic face of lupus: Focus on antigen-presenting cells.
- Author
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Wardowska A
- Subjects
- Animals, DNA Methylation, Epigenesis, Genetic, Histones metabolism, Humans, Lymphocyte Activation, RNA, Untranslated genetics, Antigen-Presenting Cells immunology, B-Lymphocytes immunology, Dendritic Cells immunology, Lupus Erythematosus, Systemic immunology, T-Lymphocytes immunology
- Abstract
In recent years, epigenetic mechanisms became widely known due to their ability to regulate and maintain physiological processes such as cell growth, development, differentiation and genomic stability. When dysregulated, epigenetic mechanisms, may introduce gene expression changes and disturbance in immune homeostasis leading to autoimmune diseases. Systemic lupus erythematosus (SLE), the most extensively studied autoimmune disorder, has already been correlated with epigenetic modifications, especially in T cells. Since these cell rely on antigen presentation, it may be assumed that erroneous activity of antigen-presenting cells (APCs), culminates in T cell abnormalities. In this review we summarize and discuss the epigenetic modifications in SLE affected APCs, with the focus on dendritic cells (DCs), B cells and monocytes. Unravelling this aspect of SLE pathogenesis, might result in identification of new disease biomarkers and putative therapeutic approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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14. Diminished mitogen-induced T cell proliferation by Trypanosoma cruzi antigens associated with antigen-presenting cell modulation and CD3 signaling.
- Author
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Gómez-Olarte S, Bolaños NI, Cuéllar A, Puerta CJ, and González JM
- Subjects
- Adult, Cell Proliferation physiology, Female, Humans, Lymphocyte Activation immunology, Male, Signal Transduction immunology, Trypanosoma cruzi, Antigen-Presenting Cells immunology, Antigens, Protozoan immunology, CD3 Complex immunology, Chagas Disease immunology, T-Lymphocytes immunology
- Abstract
Chronic infection by Trypanosoma cruzi decreases T cell proliferation and it is most likely accompanied by changes in signals required for activation. We assessed the effect of T. cruzi antigens on mitogen-induced proliferation of T cells from uninfected individuals and the association with the expression of molecules involved in antigen presentation, T cell costimulation and activation, and cytokine production. T. cruzi antigen exposure reduced mitogen-induced proliferation of CD4+ and CD8+ T cells in PBMC cultures, but only reduced mitogen-induced proliferation in the CD4+ T cells from sorted cell cultures cocultured with antigen-pulsed CD3- cells. CD40/CD80 and CD86 expression were reduced in antigen-pulsed DCs and monocytes, respectively. TNF-α, IL-10 and CCL17 levels were increased in cultures with antigen-pulsed CD3- cells, while CD3ζ chain expression was reduced in T cells from cultures with antigen. Our findings suggest that T. cruzi could alter T cell proliferation indirectly by downregulating costimulatory molecules and inducing the secretion of IL-10 and directly by decreasing TCR signaling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
15. Augmentation of T-Cell Activation by Oscillatory Forces and Engineered Antigen-Presenting Cells.
- Author
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Majedi FS, Hasani-Sadrabadi MM, Thauland TJ, Li S, Bouchard LS, and Butte MJ
- Subjects
- Animals, Antigen-Presenting Cells cytology, Artificial Cells cytology, Biomechanical Phenomena, Cells, Cultured, Humans, Mice, Receptors, Antigen, T-Cell immunology, T-Lymphocytes cytology, Antigen-Presenting Cells immunology, Artificial Cells immunology, Lymphocyte Activation, T-Lymphocytes immunology
- Abstract
Activation of T cells by antigen presenting cells (APCs) initiates their proliferation, cytokine production, and killing of infected or cancerous cells. We and others have shown that T-cell receptors require mechanical forces for triggering, and these forces arise during the interaction of T cells with APCs. Efficient activation of T cells in vitro is necessary for clinical applications. In this paper, we studied the impact of combining mechanical, oscillatory movements provided by an orbital shaker with soft, biocompatible, artificial APCs (aAPCs) of various sizes and amounts of antigen. We showed that these aAPCs allow for testing the strength of signal delivered to T cells, and enabled us to confirm that that absolute amounts of antigen engaged by the T cell are more important for activation than the density of antigen. We also found that when our aAPCs interact with T cells in the context of an oscillatory mechanoenvironment, they roughly double antigenic signal strength, compared to conventional, static culture. Combining these effects, our aAPCs significantly outperformed the commonly used Dynabeads. We finally demonstrated that tuning the signal strength down to a submaximal "sweet spot" allows for robust expansion of induced regulatory T cells. In conclusion, augmenting engineered aAPCs with mechanical forces offers a novel approach for tuning of T-cell activation and differentiation.
- Published
- 2019
- Full Text
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16. Abatacept for the treatment of psoriatic arthritis.
- Author
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Lubrano E, Scriffignano S, and Perrotta FM
- Subjects
- Animals, CTLA-4 Antigen metabolism, Cell Communication drug effects, Clinical Trials as Topic, Drug Evaluation, Preclinical, Humans, Abatacept therapeutic use, Antigen-Presenting Cells immunology, Arthritis, Psoriatic drug therapy, Lymphocytes immunology
- Abstract
Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by the presence of psoriasis, arthritis, and enthesitis, with the association of other musculoskeletal and extra-articular manifestations. Current treatment of PsA is based on the use of conventional, biological and targeted synthetic disease modifying anti-rheumatic drugs; however, patients may not respond or have a loss of response to these agents. Recently, a deeper understanding of the pathogenetic mechanisms has made possible the development of new drugs that actively interact with the activation of immune system, inhibiting the co-stimulation between antigen-presenting cells and lymphocytes. Areas covered: The aim of this paper is to review the role of the activation of the immune system in the pathogenesis and treatment of PsA, with a discussion on the emerging CTLA4Ig drugs (abatacept) for PsA. A search in PubMed and EMBASE was performed with the keywords: 'abatacept', 'CTLA4,' and 'Psoriatic Arthritis.' We considered preclinical studies, phase I, II and III clinical trials. Expert commentary: The inhibitors of co-stimulation may represent an effective treatment strategy by acting on the very early phase of the immunological process that brought about the development of inflammation and activation of the immune system, mainly for patients with peripheral joint involvement and mild psoriasis.
- Published
- 2018
- Full Text
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17. A simulation of the random and directed motion of dendritic cells in chemokine fields.
- Author
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Parr, Avery, Anderson, Nicholas R., and Hammer, Daniel A.
- Subjects
DENDRITIC cells ,CHEMOTAXIS ,CHEMOKINE receptors ,CELL receptors ,ANTIGEN presenting cells ,T cells ,MOTION - Abstract
Dendritic cells (DCs) are the most effective professional antigen-presenting cell. They ferry antigen from the extremities to T cells and are essential for the initiation of an adaptive immune response. Despite interest in how DCs respond to chemical stimuli, there have been few attempts to model DC migration. In this paper, we simulate the motility of DCs by modeling the generation of forces by filopodia and a force balance on the cell. The direction of fliopodial extension is coupled to differential occupancy of cognate chemokine receptors across the cell. Our model simulates chemokinesis and chemotaxis in a variety of chemical and mechanical environments. Simulated DCs undergoing chemokinesis were measured to have a speed of 5.1 ± 0.07 μm·min
-1 and a persistence time of 3.2 ± 0.46 min, consistent with experiment. Cells undergoing chemotaxis exhibited a stronger chemotactic response when exposed to lower average chemokine concentrations, also consistent with experiment. We predicted that when placed in two opposing gradients, cells will cluster in a line, which we call the “line of equistimulation;” this clustering has also been observed. We calculated the effect of varying gradient steepness on the line of equistimulation, with steeper gradients resulting in tighter clustering. Moreover, gradients are found to be most potent when cells are in a gradient of chemokine whose mean concentration is close to the binding of the Kd to the receptor, and least potent when the mean concentration is 0.1Kd . Comparing our simulations to experiment, we can give a quantitative measure of the strength of certain chemokines relative to others. Assigning the signal of CCL19 binding CCR7 a baseline strength of 1, we found CCL21 binding CCR7 had a strength of 0.28, and CXCL12 binding CXCR4 had a strength of 0.30. These differences emerge despite both chemokines having virtually the same Kd , suggesting a mechanism of signal amplification in DCs requiring further study. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
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18. A Non‐Coding Oligonucleotide Recruits Cutaneous CD11b+ Cells that Inhibit Thelper Responses and Promote Tregs.
- Author
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Kamal, Kahkashan, Richardsdotter‐Andersson, Elina, Dondalska, Aleksandra, Wahren‐Herlenius, Marie, and Spetz, Anna‐Lena
- Subjects
REGULATORY T cells ,IMMUNE checkpoint proteins ,T helper cells ,T cells ,IMMUNOLOGICAL tolerance - Abstract
Skin‐resident antigen‐presenting cells (APC) play an important role in maintaining peripheral tolerance via immune checkpoint proteins and induction of T regulatory cells (Tregs). However, there is a lack of knowledge on how to expand or recruit immunoregulatory cutaneous cells without causing inflammation. Here, it is shown that administration of a non‐coding single‐stranded oligonucleotide (ssON) leads to CCR2‐dependent accumulation of CD45+CD11b+Ly6C+ cells in the skin that express substantial levels of PD‐L1 and ILT3. Transcriptomic analyses of skin biopsies reveal the upregulation of key immunosuppressive genes after ssON administration. Functionally, the cutaneous CD11b+ cells inhibit Th1/2/9 responses and promote the induction of CD4+FoxP3+ T‐cells. In addition, ssON treatment of imiquimod‐induced inflammation results in significantly reduced Th17 responses. It is also shown that induction of IL‐10 production in the presence of cutaneous CD11b+ cells isolated after ssON administrations is partly PD‐L1 dependent. Altogether, an immunomodulatory ssON is identified that can be used therapeutically to recruit cutaneous CD11b+ cells with the capacity to dampen Th cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. In vitro uptake of oligomannose-coated liposomes leads to differentiation of inflammatory monocytes into mature antigen-presenting cells that can activate T cells.
- Author
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Matsuoka Y, Kawauchi Y, Kuroda Y, Kawauchi K, and Kojima N
- Subjects
- Animals, Antigens metabolism, Cell Differentiation, Cells, Cultured, Female, Humans, Liposomes chemistry, Lymphocyte Activation, Mannose chemistry, Mice, Mice, Inbred C57BL, Ovalbumin metabolism, Antigen-Presenting Cells physiology, Liposomes metabolism, Monocytes physiology, Th1 Cells immunology
- Abstract
Oligomannose-coated liposomes (OMLs), containing entrapped antigens, serve as effective antigen delivery vehicles and as a novel adjuvant to induce antigen-specific cellular immune responses. However, in vitro activation of antigen-presenting cells (APCs) by OMLs has not yet been demonstrated. In this paper, we found that OMLs can deliver the antigens and the stimulatory signals into inflammatory monocytes in vitro, leading to differentiation of the cells to mature APCs. When OMLs were co-cultured with peripheral blood mononuclear cells from C57BL/6 mice in the presence of mouse serum, OMLs were preferentially incorporated into both Ly6C
high monocytes and Ly6Clow monocytes, which are referred to as murine inflammatory and resident monocytes, respectively. The expression of CD11c, CD80, CD86, CCR7, and MHC class II on the Ly6Chigh monocytes was significantly enhanced during the 24 h after OML uptake, whereas upregulation of these molecules on the Ly6Clow monocytes was limited. In addition, the antigenic peptide of OVA encased in OMLs was presented on MHC class I of only Ly6Chigh monocytes. Furthermore, OVA-encasing OML-ingesting monocytes can activate CD8+ T cells from OT-1 mice, suggesting that antigens encapsulated in OMLs were cross-presented in inflammatory monocytes. Adoptive transfer of the monocytes that engulf OVA-encasing OMLs led to induction of an antigen-specific Th1 immune response in mice. Taken together, mature APCs can be generated from inflammatory monocytes in peripheral blood by ex vivo treatment of the cells with OMLs without any additional stimuli., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
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20. A minimally invasive optical trapping system to understand cellular interactions at onset of an immune response.
- Author
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Glass DG, McAlinden N, Millington OR, and Wright AJ
- Subjects
- Calibration, Antigen-Presenting Cells immunology, Cell Communication, Optical Tweezers, T-Lymphocytes immunology
- Abstract
T-cells and antigen presenting cells are an essential part of the adaptive immune response system and how they interact is crucial in how the body effectively fights infection or responds to vaccines. Much of the experimental work studying interaction forces between cells has looked at the average properties of bulk samples of cells or applied microscopy to image the dynamic contact between these cells. In this paper we present a novel optical trapping technique for interrogating the force of this interaction and measuring relative interaction forces at the single-cell level. A triple-spot optical trap is used to directly manipulate the cells of interest without introducing foreign bodies such as beads to the system. The optical trap is used to directly control the initiation of cell-cell contact and, subsequently to terminate the interaction at a defined time point. The laser beam power required to separate immune cell pairs is determined and correlates with the force applied by the optical trap. As proof of concept, the antigen-specific increase in interaction force between a dendritic cell and a specific T-cell is demonstrated. Furthermore, it is demonstrated that this interaction force is completely abrogated when T-cell signalling is blocked. As a result the potential of using optical trapping to interrogate cellular interactions at the single cell level without the need to introduce foreign bodies such as beads is clearly demonstrated.
- Published
- 2017
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21. Trends in multimorbidity and polypharmacy in the Flemish-Belgian population between 2000 and 2015.
- Author
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van den Akker, Marjan, Vaes, Bert, Goderis, Geert, Van Pottelbergh, Gijs, De Burghgraeve, Tine, and Henrard, Séverine
- Subjects
COMORBIDITY ,POLYPHARMACY ,REGRESSION analysis ,CYTOLOGY ,EPIDEMIOLOGY - Abstract
Objectives: The aim of this paper was to describe the time trends in the prevalence of multimorbidity and polypharmacy in Flanders (Belgium) between 2000 and 2015, while controlling for age and sex. Methods: Data were available from Intego, a Flemish-Belgian general practice-based morbidity registration network. The practice population between 2000 and 2015 was used as the denominator, representing a mean of 159,946 people per year. Age and gender-standardised prevalence rates were used for the trends of multimorbidity and polypharmacy in the total population and for subgroups. Joinpoint regression analyses were used to analyse the time trends and breaks in trends, for the entire population as well as for specific age and sex groups. Results: Overall, in 2015, 22.7% of the population had multimorbidity, while the overall prevalence of polypharmacy was 20%. Throughout the study period the standardised prevalence rate of multimorbidity rose for both sexes and in all age groups. The largest relative increase in multimorbidity was observed in the younger age groups (up to the age of 50 years). The prevalence of polypharmacy showed a significant increase between 2000 and 2015 for all age groups except the youngest (0–25 years). Conclusion: For all adult age groups multimorbidity and polypharmacy are frequent, dynamic over time and increasing. This asks for both epidemiological and interventional studies to improve the management of the resulting complex care. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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22. MyD88/CD40 Genetic Adjuvant Function in Cutaneous Atypical Antigen-Presenting Cells Contributes to DNA Vaccine Immunogenicity.
- Author
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Collinson-Pautz MR, Slawin KM, Levitt JM, and Spencer DM
- Subjects
- Animals, Antigen-Presenting Cells cytology, Antigen-Presenting Cells metabolism, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cancer Vaccines immunology, Cancer Vaccines therapeutic use, Cell Line, Cell Proliferation, Cytokines analysis, Cytokines metabolism, Female, Genetic Vectors genetics, Genetic Vectors metabolism, Keratinocytes cytology, Keratinocytes metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, MicroRNAs antagonists & inhibitors, MicroRNAs genetics, MicroRNAs metabolism, NIH 3T3 Cells, Neoplasms immunology, Neoplasms therapy, Vaccines, DNA therapeutic use, Antigen-Presenting Cells immunology, CD40 Antigens genetics, Myeloid Differentiation Factor 88 genetics, Vaccines, DNA immunology
- Abstract
Therapeutic DNA-based vaccines aim to prime an adaptive host immune response against tumor-associated antigens, eliminating cancer cells primarily through CD8+ cytotoxic T cell-mediated destruction. To be optimally effective, immunological adjuvants are required for the activation of tumor-specific CD8+ T cells responses by DNA vaccination. Here, we describe enhanced anti-tumor efficacy of an in vivo electroporation-delivered DNA vaccine by inclusion of a genetically encoded chimeric MyD88/CD40 (MC) adjuvant, which integrates both innate and adaptive immune signaling pathways. When incorporated into a DNA vaccine, signaling by the MC adjuvant increased antigen-specific CD8+ T cells and promoted elimination of pre-established tumors. Interestingly, MC-enhanced vaccine efficacy did not require direct-expression of either antigen or adjuvant by local antigen-presenting cells, but rather our data supports a key role for MC function in "atypical" antigen-presenting cells of skin. In particular, MC adjuvant-modified keratinocytes increased inflammatory cytokine secretion, upregulated surface MHC class I, and were able to increase in vitro and in vivo priming of antigen-specific CD8+ T cells. Furthermore, in the absence of critical CD8α+/CD103+ cross-priming dendritic cells, MC was still able to promote immune priming in vivo, albeit at a reduced level. Altogether, our data support a mechanism by which MC signaling activates an inflammatory phenotype in atypical antigen-presenting cells within the cutaneous vaccination site, leading to an enhanced CD8+ T cell response against DNA vaccine-encoded antigens, through both CD8α+/CD103+ dendritic cell-dependent and independent pathways., Competing Interests: DMS and KMS are both officers and shareholders of Bellicum Pharmaceuticals, a publicly held biopharmaceutical company, and have significant financial competing interest in the underlying technology discussed in this paper (US Patent Publication Number US20100203067 A1). MRC was partially supported by a financial gift to Baylor College of Medicine from Bellicum Pharmaceuticals. However, this does not alter our adherence to PLOS ONE policies on sharing data and materials, as outlined in http://www.PLOSone.org/static/editorial.action#competing.
- Published
- 2016
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23. Combination therapy for cancer with oncolytic virus and checkpoint inhibitor: A mathematical model.
- Author
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Friedman, Avner and Lai, Xiulan
- Subjects
CANCER cells ,CANCER treatment ,IMMUNE response ,MATHEMATICAL models ,COMBINATION drug therapy - Abstract
Oncolytic virus (OV) is a replication competent virus that selectively invades cancer cells; as these cells die under the viral burden, the released virus particles proceed to infect other cancer cells. Oncolytic viruses are designed to also be able to stimulate the anticancer immune response. Thus, one may represent an OV by two parameters: its replication potential and its immunogenicity. In this paper we consider a combination therapy with OV and a checkpoint inhibitor, anti-PD-1. We evaluate the efficacy of the combination therapy in terms of the tumor volume at some later time, for example, 6 months from initial treatment. Since T cells kill not only virus-free cancer cells but also virus-infected cancer cells, the following question arises: Does increasing the amount of the checkpoint inhibitor always improve the efficacy? We address this question, by a mathematical model consisting of a system of partial differential equations. We use the model to construct, by simulations, an efficacy map in terms of the doses of the checkpoint inhibitor and the OV injection. We show that there are regions in the map where an increase in the checkpoint inhibitor actually decreases the efficacy of the treatment. We also construct efficacy maps with checkpoint inhibitor vs. the replication potential of the virus that show the same antagonism, namely, an increase in the checkpoint inhibitor may actually decrease the efficacy. These results have implications for clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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- View/download PDF
24. Forced expression of IL-7R promotes CD8 T cell cytotoxicity to self antigen.
- Author
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Peng, YuFeng
- Subjects
INTERLEUKIN-7 receptors ,CYTOTOXIC T cells ,CD8 antigen ,PROTEIN expression ,DENDRITIC cells - Abstract
Cross-presentation of apoptotic cell associated antigens by immature dendritic cells prevents the activation of self reactive CD8 T cells. Tolerized self reactive CD8 T cells down-regulate IL-7R expression on their surface. Whether over-expression of IL-7R can reverse their fate and function has not been examined. In this paper, we showed forced expression of IL-7R in OT-I T cells by a transgene enhanced CD8 T cell mediated diabetes in the RIP-mOVA model. Although IL-7R Tg (transgenic) did not completely reverse the deletion of OT-I T cells, it provided a significant survival advantage over w.t OT-I T cells. Furthermore, IL7R Tg OT-I T cells isolated from diabetic pancreata displayed increased production of IFN-γ, higher expression of T-bet, and increased externalization of CD107a. We also found that immature DCs containing apoptotic cells expressed high levels of PDL-1 on their surface. Although IL-7R Tg did not change PD1 expression on activated OT-I cells in vivo, the transgene enabled a significantly lower number of OT-I T cells to induce diabetes in the absence of PDL-1. Our results demonstrated that forced expression of IL-7R not only improved the functionality of tolerized CD8 T cells, it also acted in synergy with PDL-1 deficiency to further promote CD8 T cell cytotoxicity to self antigens. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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- View/download PDF
25. Enhancement of SARS-CoV-2 mRNA Vaccine Efficacy through the Application of TMSB10 UTR for Superior Antigen Presentation and Immune Activation.
- Author
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Ding, Xiaoyan, Zhou, Yuxin, He, Jiuxiang, Zhao, Jing, and Li, Jintao
- Subjects
COVID-19 vaccines ,VACCINE effectiveness ,ANTIGEN presentation ,SARS-CoV-2 Delta variant ,HUMORAL immunity ,REPORTER genes - Abstract
The development of effective vaccines against SARS-CoV-2 remains a critical challenge amidst the ongoing global pandemic. This study introduces a novel approach to enhancing mRNA vaccine efficacy by leveraging the untranslated region (UTR) of TMSB10, a gene identified for its significant mRNA abundance in antigen-presenting cells. Utilizing the GEO database, we identified TMSB10 among nine genes, with the highest mRNA abundance in dendritic cell subtypes. Subsequent experiments revealed that TMSB10's UTR significantly enhances the expression of a reporter gene in both antigen-presenting and 293T cells, surpassing other candidates and a previously optimized natural UTR. A comparative analysis demonstrated that TMSB10 UTR not only facilitated a higher reporter gene expression in vitro but also showed marked superiority in vivo, leading to enhanced specific humoral and cellular immune responses against the SARS-CoV-2 Delta variant RBD antigen. Specifically, vaccines incorporating TMSB10 UTR induced significantly higher levels of specific IgG antibodies and promoted a robust T-cell immune response, characterized by the increased secretion of IFN-γ and IL-4 and the proliferation of CD4
+ and CD8+ T cells. These findings underscore the potential of TMSB10 UTR as a strategic component in mRNA vaccine design, offering a promising avenue to bolster vaccine-induced immunity against SARS-CoV-2 and, potentially, other pathogens. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
26. CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity.
- Author
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Pereira CS and Macedo MF
- Subjects
- Adaptive Immunity immunology, Antigen Presentation immunology, Antigens, CD1 genetics, Antigens, CD1d genetics, Glycoproteins genetics, Humans, Immunity, Innate immunology, Antigen-Presenting Cells immunology, Antigens, CD1 immunology, Antigens, CD1d immunology, Glycoproteins immunology, Natural Killer T-Cells immunology
- Abstract
Lipid-specific T cells comprise a group of T cells that recognize lipids bound to the MHC class I-like CD1 molecules. There are four isoforms of CD1 that are expressed at the surface of antigen presenting cells and therefore capable of presenting lipid antigens: CD1a, CD1b, CD1c, and CD1d. Each one of these isoforms has distinct structural features and cellular localizations, which promotes binding to a broad range of different types of lipids. Lipid antigens originate from either self-tissues or foreign sources, such as bacteria, fungus, or plants and their recognition by CD1-restricted T cells has important implications in infection but also in cancer and autoimmunity. In this review, we describe the characteristics of CD1 molecules and CD1-restricted lipid-specific T cells, highlighting the innate-like and adaptive-like features of different CD1-restricted T cell subtypes., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.
- Published
- 2016
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- View/download PDF
27. Chitosan as an Immunomodulating Adjuvant on T-Cells and Antigen-Presenting Cells in Herpes Simplex Virus Type 1 Infection.
- Author
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Choi B, Jo DH, Anower AK, Islam SM, and Sohn S
- Subjects
- Animals, Antibodies, Viral immunology, Crustacea, Dendritic Cells cytology, Enzyme-Linked Immunosorbent Assay, Green Fluorescent Proteins metabolism, Immunoglobulin G immunology, Leukocytes, Mononuclear cytology, Male, Mice, Mice, Inbred ICR, Monocytes cytology, Receptors, Interleukin-15 metabolism, Receptors, Interleukin-7 metabolism, T-Lymphocytes cytology, Adjuvants, Immunologic chemistry, Antigen-Presenting Cells drug effects, Chitosan chemistry, Herpes Simplex immunology, Herpesvirus 1, Human
- Abstract
Herpes disease caused by herpes simplex virus type 1 (HSV-1) is an intractable condition. It is a major concern in public health. Our purpose of this study was to verify the function of chitosan as an adjuvant for immune regulation specifically under herpes simplex virus type 1 (HSV-1) infection. Ahead of HSV infection, chitosan, heat inactivated green fluorescent protein expressing HSV (G-HSV), and a combination of chitosan and G-HSV were used to pretreat ICR mice followed by HSV-1 infection. Using flow cytometric analysis, the frequencies of T-cells, monocytes, dendritic cells (DCs), and natural killer (NK) cells were analyzed by surface expression of CD4
+ , CD8+ , CD14+ , CD11c+ , NK1.1+ , and DX5+ cells. In HSV infected mice, chitosan treatment significantly increased the frequencies of CD4+ T-cells (33.6 ± 5.78%) compared to those in the control group (24.02 ± 12.47%, p = 0.05). The frequencies of DC and NK cells were also significantly different between chitosan treated mice and control mice. In addition, anti-HSV IgG antibody was downregulated in chitosan treated mice. These results suggest that chitosan is a potential modulator or immune stimulator as an adjuvant in HSV-1 infected mice., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.- Published
- 2016
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- View/download PDF
28. Effects of artemisinin and cisplatin on the malignant progression of oral leukoplakia. In vitro and in vivo study
- Author
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Dutra, Mateus José, Malta, Isabella Souza, de Almeida Lança, Maria Leticia, de Vasconcellos, Luana Marotta Reis, Adorno-Farias, Daniela, Jara, José Antonio, and Kaminagakura, Estela
- Published
- 2024
- Full Text
- View/download PDF
29. Generic, scalable and decentralized fault detection for robot swarms.
- Author
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Tarapore, Danesh, Christensen, Anders Lyhne, and Timmis, Jon
- Subjects
ROBOTS ,DECENTRALIZED control systems ,AUTOMATIC control systems ,SCALABILITY ,ROBUST control - Abstract
Robot swarms are large-scale multirobot systems with decentralized control which means that each robot acts based only on local perception and on local coordination with neighboring robots. The decentralized approach to control confers number of potential benefits. In particular, inherent scalability and robustness are often highlighted as key distinguishing features of robot swarms compared with systems that rely on traditional approaches to multirobot coordination. It has, however, been shown that swarm robotics systems are not always fault tolerant. To realize the robustness potential of robot swarms, it is thus essential to give systems the capacity to actively detect and accommodate faults. In this paper, we present a generic fault-detection system for robot swarms. We show how robots with limited and imperfect sensing capabilities are able to observe and classify the behavior of one another. In order to achieve this, the underlying classifier is an immune system-inspired algorithm that learns to distinguish between normal behavior and abnormal behavior online. Through a series of experiments, we systematically assess the performance of our approach in a detailed simulation environment. In particular, we analyze our system’s capacity to correctly detect robots with faults, false positive rates, performance in a foraging task in which each robot exhibits a composite behavior, and performance under perturbations of the task environment. Results show that our generic fault-detection system is robust, that it is able to detect faults in a timely manner, and that it achieves a low false positive rate. The developed fault-detection system has the potential to enable long-term autonomy for robust multirobot systems, thus increasing the usefulness of robots for a diverse repertoire of upcoming applications in the area of distributed intelligent automation. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
30. Antigen Presenting Properties of a Myeloid Dendritic-Like Cell in Murine Spleen.
- Author
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Hey, Ying-ying and O’Neill, Helen C.
- Subjects
LYMPHOID tissue ,HEMATOPOIETIC system ,DENDRITIC cells ,PHENOTYPES ,T cells - Abstract
This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named “L-DC” since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11b
hi CD11clo MHCII- CD43+ Ly6C- Ly6G- Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
31. Refining Pathways: A Model Comparison Approach.
- Author
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Moffa, Giusi, Erdmann, Gerrit, Voloshanenko, Oksana, Hundsrucker, Christian, Sadeh, Mohammad J., Boutros, Michael, and Spang, Rainer
- Subjects
CELLULAR signal transduction ,MOLECULAR interactions ,SYSTEMS biology ,COMPUTATIONAL biology ,GENETIC mutation - Abstract
Cellular signalling pathways consolidate multiple molecular interactions into working models of signal propagation, amplification, and modulation. They are described and visualized as networks. Adjusting network topologies to experimental data is a key goal of systems biology. While network reconstruction algorithms like nested effects models are well established tools of computational biology, their data requirements can be prohibitive for their practical use. In this paper we suggest focussing on well defined aspects of a pathway and develop the computational tools to do so. We adapt the framework of nested effect models to focus on a specific aspect of activated Wnt signalling in HCT116 colon cancer cells: Does the activation of Wnt target genes depend on the secretion of Wnt ligands or do mutations in the signalling molecule β-catenin make this activation independent from them? We framed this question into two competing classes of models: Models that depend on Wnt ligands secretion versus those that do not. The model classes translate into restrictions of the pathways in the network topology. Wnt dependent models are more flexible than Wnt independent models. Bayes factors are the standard Bayesian tool to compare different models fairly on the data evidence. In our analysis, the Bayes factors depend on the number of potential Wnt signalling target genes included in the models. Stability analysis with respect to this number showed that the data strongly favours Wnt ligands dependent models for all realistic numbers of target genes. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
32. CD40L--a costimulatory molecule involved in the maturation of antigen presenting cells in Atlantic salmon (Salmo salar).
- Author
-
Lagos LX, Iliev DB, Helland R, Rosemblatt M, and Jørgensen JB
- Subjects
- Amino Acid Sequence, Animals, Antigen-Presenting Cells metabolism, CD40 Antigens biosynthesis, CD40 Antigens chemistry, CD40 Ligand chemistry, CD40 Ligand metabolism, Concanavalin A immunology, Dinucleoside Phosphates immunology, Head Kidney cytology, Head Kidney immunology, Lymphocyte Activation, Molecular Sequence Data, Phylogeny, Phytohemagglutinins immunology, Protein Structure, Tertiary, Salmo salar genetics, Sequence Alignment, Antigen-Presenting Cells immunology, CD40 Antigens immunology, CD40 Ligand immunology, Leukocytes immunology, Salmo salar immunology
- Abstract
The CD40L/CD40 signalling pathway is critically involved in the final stage of the maturation of DCs. This paper reports the identification and functional characterization of CD40L and CD40 from Atlantic salmon (Salmo salar). Salmon CD40L is a type II membrane-bound protein with a TNF homology domain in its extracellular C-terminal region, while CD40 is a type I membrane-bound receptor with a sequence pattern of four cysteine-rich domains in its extracellular N-terminal region. The salmon CD40L and CD40 were widely expressed, particularly in immune tissues, and while CD40L expression was induced by in vitro stimulation of HKLs with PHA and ConA, CpG increased CD40 expression. A CD40L construct was overexpressed in the CHSE-214 cell line and co-cultivation of the CD40L-CHSE transfectants with HKL induced a rapid and long-lasting upregulation of important costimulatory molecules like CD40, CD83, B7-H1 and the cytokines IL-12p40, IL-10, IL-1β and IFNs, which all are involved in T-helper cell responses. Furthermore, the CD40L transfected cells increased the percentage of HKLs expressing surface MHCIIβ but unlike other APC maturation stimuli, like CpG, they did not reduce the capacity to internalise antigen. Our results provide the first evidence for the existence of a functional CD40L mediated costimulatory pathway in Atlantic salmon., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
33. Antigen presenting cells costimulatory signaling during pre-implantation pregnancy.
- Author
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Sławek A, Maj T, and Chełmonska-Soyta A
- Subjects
- Cell Communication immunology, Cytokines immunology, Dendritic Cells immunology, Female, Hormones metabolism, Humans, Intercellular Signaling Peptides and Proteins, Interleukin-2, Lymphocytes immunology, Receptor Cross-Talk immunology, Semen immunology, Signal Transduction immunology, Antigen-Presenting Cells immunology, Antigens, CD immunology, Embryonic Development immunology, Immune Tolerance immunology, Pregnancy immunology
- Abstract
Success of pregnancy depends on many factors. Three phenomena inducing immune tolerance against semi-allogeneic conceptus may play a crucial role in the pre-implantation period of pregnancy: influence of sex hormones in sex cycle, presence of oocyte or embryo and the presence of semen in the female reproductive tract. On the other hand dendritic cells are the most effective antigen-presenting cells in regulation of immune phenomena and also are considered as potent participants in inducing immune tolerance in the pregnancy. They communicate with T cells in cell contact-dependent manner or via cytokines. During cell-cell contacts, costimulatory molecules play a key role and their expression is often dependent on cytokines milieu. Both costimulatory molecules and cytokines influence generation of T regulatory cells. Interactions of these molecules are closely related. In this paper we would like to pay attention to the importance of antigen presenting cells costimulatory potency in immune regulation during a pre-implantation period of pregnancy.
- Published
- 2012
- Full Text
- View/download PDF
34. Generation of antigen-specific cytotoxic T lymphocytes using a leukemic plasmacytoid dendritic cell line as antigen presenting cells.
- Author
-
Yamahira A, Narita M, Nakamura T, Watanabe N, Kaji M, Taniguchi T, Hashimoto S, Furukawa T, Toba K, Aizawa Y, Kuzushima K, and Takahashi M
- Subjects
- Antigen Presentation drug effects, Antigen Presentation immunology, Antigen-Presenting Cells metabolism, Antigens metabolism, Antigens, Viral immunology, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cell Line, Tumor, Cells, Cultured, Coculture Techniques, Dendritic Cells metabolism, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunophenotyping, Immunotherapy, Adoptive methods, Interleukin-12 immunology, Interleukin-12 metabolism, Leukemia immunology, Leukemia metabolism, Leukemia pathology, Lipopolysaccharides pharmacology, Peptide Fragments immunology, Phosphoproteins immunology, T-Lymphocytes, Cytotoxic metabolism, Tumor Necrosis Factor-alpha immunology, Tumor Necrosis Factor-alpha metabolism, Viral Matrix Proteins immunology, WT1 Proteins immunology, Antigen-Presenting Cells immunology, Antigens immunology, Dendritic Cells immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Establishment of a leukemia plasmacytoid dendritic cell line (PMDC05) and intra-lineage transformation from pDCs to mDCs in PMDC05 has been reported. In this paper, we show the applicability of PMDC05 for cellular immunotherapy. By stimulation with LPS, PMDC05 showed enhancement in expression of antigen presentation-associated surface molecules and production of cytokines (IL-12p70 and TNF-α). The antigen presenting ability was markedly increased in PMDC05 stimulated with LPS. By co-culturing of CD8(+) T cells with LPS-stimulated and WT1/CMVpp65 peptide-pulsed PMDC05, WT1/CMVpp65 tetramer(+) cytotoxic T lymphocytes were efficiently generated. These findings reveal the applicability of PMDC05 in cellular immunotherapy for tumor and severe viral infections., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
35. Mitoksantron - antybiotyk antrachinonowy o aktywności przeciwnowotworowej stosowany w leczeniu stwardnienia rozsianego.
- Author
-
Szwed, Marzena
- Abstract
Copyright of Advances in Hygiene & Experimental Medicine / Postepy Higieny i Medycyny Doswiadczalnej is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2014
36. Single-step conjugation of bioactive peptides to proteins via a self-contained succinimidyl bis-arylhydrazone.
- Author
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Phillips JA, Morgan EL, Dong Y, Cole GT, McMahan C, Hung CY, and Sanderson SD
- Subjects
- Animals, Female, Humans, Mice, Mice, Inbred BALB C, Oligopeptides chemical synthesis, Oligopeptides immunology, Oligopeptides pharmacology, Spores, Fungal, Vaccination, Adjuvants, Immunologic chemistry, Antigen-Presenting Cells drug effects, Antigen-Presenting Cells immunology, Coccidioides immunology, Hydrazones chemistry, Interleukin-6 analysis, Niacinamide chemistry, Orthomyxoviridae immunology, Ovalbumin chemistry, Ovalbumin immunology, Serum Albumin, Bovine chemistry, Serum Albumin, Bovine immunology, Succinimides chemistry, Vaccines chemistry, Vaccines immunology
- Abstract
This paper describes a method for a single-step, site-specific conjugation of bioactive peptides to proteins that exploits the monitoring advantages provided by the unique UV signature absorbance of a bis-arylhydrazone. The utility of this method is demonstrated by the conjugation of a decapeptide molecular adjuvant, YSFKDMP(MeL)aR (EP67), to two test proteins, ovalbumin (OVA) and bovine serum albumin (BSA), and to proteins expressed on intact influenza virons and fungal arthroconidia (spores) of Coccidioides. Conjugation is accomplished with a version of EP67 in which its N-terminus is modified with succinimidyl-4-benzoylhydrazino-nicotinamide (S4BHyNic) (peptide 7), thus enabling conjugation to these large entities via formation of amide bonds with surface-exposed amino groups. The presence of the strongly absorbing bis-arylhydrazone S4BHyNic (ε(354 nm) = 29 000 L mol(-1) cm(-1)) allows for determination of EP67-to-protein molar substitution ratios (MSR), which are in good agreement with the MSRs determined by amino acid analysis. Conjugation to OVA does not compromise the ability of EP67 to engage C5a receptor bearing antigen presenting cells (APC) as measured by the EP67-mediated release of interleukin-6 (IL-6) from APCs. Mice immunized with the resulting OVA-EP67 vaccine conjugate produce high serum titers of OVA-specific IgG antibodies relative to OVA alone. Also, the conjugation of EP67 does not affect the surface integrity of influenza virons or the biological viability of Coccidioides spores. This method of conjugating bioactive peptides to proteins and other large biological entities may represent a convenient and effective way of generating various bioconjugates for use in mechanistic studies or novel therapeutic entities such as EP67-containing vaccines.
- Published
- 2009
- Full Text
- View/download PDF
37. A population dynamics analysis of the interaction between adaptive regulatory T cells and antigen presenting cells.
- Author
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Fouchet D and Regoes R
- Subjects
- Humans, Models, Theoretical, Antigen-Presenting Cells immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Background: Regulatory T cells are central actors in the maintenance of tolerance of self-antigens or allergens and in the regulation of the intensity of the immune response during infections by pathogens. An understanding of the network of the interaction between regulatory T cells, antigen presenting cells and effector T cells is starting to emerge. Dynamical systems analysis can help to understand the dynamical properties of an interaction network and can shed light on the different tasks that can be accomplished by a network., Methodology and Principal Findings: We used a mathematical model to describe a interaction network of adaptive regulatory T cells, in which mature precursor T cells may differentiate into either adaptive regulatory T cells or effector T cells, depending on the activation state of the cell by which the antigen was presented. Using an equilibrium analysis of the mathematical model we show that, for some parameters, the network has two stable equilibrium states: one in which effector T cells are strongly regulated by regulatory T cells and another in which effector T cells are not regulated because the regulatory T cell population is vanishingly small. We then simulate different types of perturbations, such as the introduction of an antigen into a virgin system, and look at the state into which the system falls. We find that whether or not the interaction network switches from the regulated (tolerant) state to the unregulated state depends on the strength of the antigenic stimulus and the state from which the network has been perturbed., Conclusion/significance: Our findings suggest that the interaction network studied in this paper plays an essential part in generating and maintaining tolerance against allergens and self-antigens.
- Published
- 2008
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38. The biological role of dectin-1 in immune response.
- Author
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Sun L and Zhao Y
- Subjects
- Animals, Antigen-Presenting Cells metabolism, Cytokines immunology, Humans, Immunity, Innate, Lectins, C-Type, Membrane Proteins chemistry, Membrane Proteins genetics, Membrane Proteins immunology, Nerve Tissue Proteins chemistry, Nerve Tissue Proteins genetics, Nerve Tissue Proteins immunology, Phagocytosis, Protein Isoforms, Signal Transduction, T-Lymphocyte Subsets metabolism, beta-Glucans immunology, Antigen-Presenting Cells immunology, Cytokines metabolism, Membrane Proteins physiology, Mycoses immunology, Nerve Tissue Proteins physiology, T-Lymphocyte Subsets immunology, beta-Glucans metabolism
- Abstract
The identification of antigen-recognizing receptors in the innate immune system significantly helped us to understand the initiation and regulation of the innate immune response. Dectin-1 was recently identified as the most important receptor for beta-glucan. Recognition of beta-glucan by dectin-1 triggers effective immune response, including phagocytosis and proinflammatory factor production, to eliminate infecting fungi, which especially benefits immunocompromised patients against opportunistic fungal infection. In addition, dectin-1 is involved in the adaptive immune response as well as autoimmune diseases and immune tolerance. In this paper, we will mainly focus on the characteristics of dectin-1 and its biological role in immune response.
- Published
- 2007
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39. A polysaccharide carrier to effectively deliver native phosphodiester CpG DNA to antigen-presenting cells.
- Author
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Shimada N, Coban C, Takeda Y, Mizu M, Minari J, Anada T, Torii Y, Shinkai S, Akira S, Ishii KJ, and Sakurai K
- Subjects
- Animals, Antigen-Presenting Cells immunology, Cells, Cultured, Cytokines blood, Cytokines immunology, DNA chemistry, Drug Carriers chemistry, Female, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Organophosphates administration & dosage, Organophosphates chemistry, Sizofiran chemistry, Spleen cytology, Toll-Like Receptor 9 deficiency, Toll-Like Receptor 9 genetics, Toll-Like Receptor 9 immunology, Antigen-Presenting Cells drug effects, CpG Islands, DNA administration & dosage, Drug Carriers administration & dosage, Sizofiran administration & dosage
- Abstract
Oligodeoxynucleotides containing unmethylated CpG sequences (CpG DNAs) activate the vertebrate innate immune system via toll-like receptor 9 (TLR-9). Although CpG DNA is a promising immunotherapeutic agent, its short circulation time in biological fluids due to nuclease is the major drawback. This paper proposes that a natural polysaccharide called schizophyllan (SPG) can be used as an effective CpG DNA carrier because SPG can complex with CpG DNA and the resultant complex shows the nuclease resistance of the bound DNA. In order to increase cellular uptake in vitro, we chemically attached spermine, cholesterol, arginine octamer, or RGD peptide to SPG. The complexes made of the chemically modified SPG and CpG DNA having a phosphorothioate (PS) or phosphodiester (PO) backbone led to increased secretion of cytokines of about 4- to 15-fold, compared with the uncomplexed dose. Furthermore, when PO CpG DNA was complexed with unmodified SPG, the IL-12 level increased by almost 3- to 11-fold compared with the naked dose. The PO CpG DNA/unmodified SPG complex data suggested that unmodified SPG might effectively deliver PO in vivo due to the electrically neutral nature of unmodified SPG. When the complexed CpG DNAs were injected intraperitoneally, a large amount of IL-12 production was observed compared with the uncomplexed material. Both in vivo and vitro assays indicated that the SPG complex may be of use for CpG DNA therapy.
- Published
- 2007
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- View/download PDF
40. A new approach for distinguishing cathepsin E and D activity in antigen-processing organelles.
- Author
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Zaidi N, Herrmann T, Baechle D, Schleicher S, Gogel J, Driessen C, Voelter W, and Kalbacher H
- Subjects
- Amino Acid Sequence, Animals, Antibody Specificity, Antigen-Presenting Cells ultrastructure, Cattle, Cell Fractionation, Cell Line, Cytosol metabolism, Endosomes metabolism, Humans, Lysosomes metabolism, Molecular Sequence Data, Substrate Specificity, Antigen-Presenting Cells metabolism, Cathepsin D metabolism, Cathepsin E metabolism, Organelles metabolism
- Abstract
Cathepsin E (CatE) and D (CatD) are the major aspartic proteinases in the endolysosomal pathway. They have similar specificity and therefore it is difficult to distinguish between them, as known substrates are not exclusively specific for one or the other. In this paper we present a substrate-based assay, which is highly relevant for immunological investigations because it detects both CatE and CatD in antigen-processing organelles. Therefore it could be used to study the involvement of these proteinases in protein degradation and the processing of invariant chain. An assay combining a new monospecific CatE antibody and the substrate, MOCAc-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(Dnp)-D-Arg-NH2[where MOCAc is (7-methoxycoumarin-4-yl)acetyl and Dnp is dinitrophenyl], is presented. This substrate is digested by both proteinases and therefore can be used to detect total aspartic proteinase activity in biological samples. After depletion of CatE by immunoprecipitation, the remaining activity is due to CatD, and the decrease in activity can be assigned to CatE. The activity of CatE and CatD in cytosolic, endosomal and lysosomal fractions of B cells, dendritic cells and human keratinocytes was determined. The data clearly indicate that CatE activity is mainly located in endosomal compartments, and that of CatD in lysosomal compartments. Hence this assay can also be used to characterize subcellular fractions using CatE as an endosomal marker, whereas CatD is a well-known lysosomal marker. The highest total aspartic proteinase activity was detected in dendritic cells, and the lowest in B cells. The assay presented exhibits a lower detection limit than common antibody-based methods without lacking the specificity.
- Published
- 2007
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41. Ternary complex consisting of DNA, polycation, and a natural polysaccharide of schizophyllan to induce cellular uptake by antigen presenting cells.
- Author
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Takeda Y, Shimada N, Kaneko K, Shinkai S, and Sakurai K
- Subjects
- Animals, Antigen-Presenting Cells metabolism, Antigens chemistry, Carbohydrate Conformation, Carbohydrate Sequence, Cell Line, CpG Islands, DNA chemistry, Drug Carriers chemistry, Electrophoresis, Gel, Two-Dimensional, Electrophoretic Mobility Shift Assay, Hydrophobic and Hydrophilic Interactions, Interleukin-12 metabolism, Macrophages metabolism, Mice, Molecular Sequence Data, Particle Size, Sizofiran chemistry, Antigen-Presenting Cells drug effects, DNA pharmacokinetics, Drug Carriers pharmacokinetics, Macrophages drug effects, Sizofiran pharmacokinetics
- Abstract
A natural polysaccharide called schizophyllan (SPG) can form a complex with polynucleotides, and the complex has been shown to deliver biofunctional short DNAs such as antisense DNAs and CpG-DNAs. Although it is a novel and efficient method, there is a drawback: attachment of homo-polynucleotide tails [for example, poly(dA) or poly(C)] to the end of DNA is necessary to stabilize the complex, because DNA heterosequences cannot bind to SPG. The aim of this paper is to present an alternative method in which SPG/DNA complexes can be made without using the tails. The basic strategy is as follows: since SPG can form hydrophobic domains in aqueous solutions, hydrophobic objects should be encapsulated by this domain. DNA alone is highly hydrophilic; however, once DNA/polycation complexes are made, they should be included by the SPG hydrophobic domain. The aim of this paper is to prove the formation of the polycation/DNA/SPG ternary complex. Gel electrophoresis showed that presence of SPG influenced the migration pattern of polycation+DNA mixtures. With increasing the SPG ratio, the zeta potential (zeta) of the polycation+DNA+SPG mixture decreased drastically to reach almost zeta = 0 and the particle size distributions were altered due to the ternary complex formation. Confocal laser scanning microscopy revealed that the polycation/DNA/SPG ternary complexes showed high uptake efficiency when the complexes were exposed to macrophage-like cells (J774.A1). IL-12 secretion was enhanced when CpG-DNA was added as the ternary complex. These features can be ascribed to the fact that J774.A1 has a SPG recognition site called Dectin-1 on the cellular surface and the ternary complex can be ingested by this pathway.
- Published
- 2007
- Full Text
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42. Utilization of the venturi effect to introduce micro-particles for epidermal vaccination.
- Author
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Liu Y
- Subjects
- Computer Simulation, Data Interpretation, Statistical, Drug Delivery Systems, Gases, Humans, Particle Size, Antigen-Presenting Cells immunology, Biolistics methods, Epidermis immunology, Vaccination methods, Vaccines, DNA administration & dosage
- Abstract
Skin represents a potent immunological induction site, with a dense network of special antigen-presenting cells (APCs) in the epidermal layer. DNA vaccination targeting APCs offers a promising new therapeutic intervention for a wide range of diseases. A unique biomedical device, the venturi powdered injection system (venturi), is proposed for the epidermal delivery of DNA vaccines. The novelty of this hand-held venturi device is in using the venturi effect to entrain DNA-coated micro-particles into an established quasi-steady transonic helium flow and accelerate them to an appropriate momentum for penetrating the skin or mucosal tissue to achieve an immunological effect. In this paper, computational fluid dynamics (CFD) has been employed to scrutinize an experimental venturi device. Key features of gas dynamics and gas-particle interactions have been presented. A parallel extension was added to improve the uniformity of gas and particle flow for a better particle penetration distribution. The overall capability of the venturi biolistic configuration for delivering micro-particles has been explored and discussed. Statistical analysis has shown that the modelled micro-particles have achieved a mean velocity of 654m/s for intracellular DNA vaccine delivery applications.
- Published
- 2007
- Full Text
- View/download PDF
43. Ito cells, stellate cells, and myofibroblasts: new actors in antigen presentation.
- Author
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Unanue ER
- Subjects
- Animals, Fibroblasts immunology, Humans, Liver cytology, Antigen Presentation immunology, Antigen-Presenting Cells cytology, Antigen-Presenting Cells immunology, Fibroblasts cytology, Liver immunology
- Abstract
Winau et al. provide convincing evidence that liver stellate cells can be antigen-presenting cells. This paper raises the following question: what are the roles and importance of diverse antigen-presenting cells in different organs?
- Published
- 2007
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- View/download PDF
44. Expression of TOLL-like receptors (TLR) by bovine antigen-presenting cells-potential role in pathogen discrimination?
- Author
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Werling D, Piercy J, and Coffey TJ
- Subjects
- Animals, Cattle genetics, Cattle microbiology, Cattle Diseases immunology, Cattle Diseases microbiology, Immunity, Innate, In Vitro Techniques, Macrophages immunology, Macrophages microbiology, Mycobacterium Infections immunology, Mycobacterium Infections microbiology, Mycobacterium Infections veterinary, RNA, Messenger genetics, RNA, Messenger metabolism, Toll-Like Receptors chemistry, Toll-Like Receptors genetics, Antigen-Presenting Cells immunology, Cattle immunology, Toll-Like Receptors metabolism
- Abstract
Invading pathogens are controlled by the innate and adaptive arms of the immune system. Adaptive immunity, mediated by B and T lymphocytes, recognises pathogens via high affinity receptors. However, the establishment of a primary adaptive immune response is not rapid enough to eradicate invading microorganisms as it involves cell proliferation, gene activation and protein synthesis. More rapid defence mechanisms are provided by innate immunity, which recognises invading pathogens by germ-line-encoded pattern recognition receptors. Recent evidence shows that this recognition can mainly be attributed to the family of TOLL-like receptors (TLR). Binding of pathogen-associated molecular patterns to TLR induces the production of reactive oxygen and nitrogen intermediates, pro-inflammatory cytokines, and up-regulates expression of co-stimulatory molecules, subsequently initiating the adaptive immunity. In this paper, we will discuss the current knowledge with regards to the TLR, and in particular the bovine family of TLR. In addition, we will show the expression of TLR mRNA in bovine antigen-presenting cell subsets, summarise the discovery and the critical roles of TLR2 in host defence against Mycobacteria, and provide evidence for a mycobacteria species-specific response of bovine macrophages.
- Published
- 2006
- Full Text
- View/download PDF
45. CD4+ T lymphocytes expressing CD40 ligand help the IgM antibody response to soluble pneumococcal polysaccharides via an intermediate cell type.
- Author
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Jeurissen A, Billiau AD, Moens L, Shengqiao L, Landuyt W, Wuyts G, Boon L, Waer M, Ceuppens JL, and Bossuyt X
- Subjects
- Animals, Antigen-Presenting Cells metabolism, B-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD40 Antigens immunology, CD40 Antigens metabolism, CD40 Ligand metabolism, Cell Communication immunology, Enzyme-Linked Immunosorbent Assay, Immunoglobulin M blood, Immunoglobulin M immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Streptococcus pneumoniae immunology, Antigen-Presenting Cells immunology, Bacterial Capsules immunology, CD4-Positive T-Lymphocytes immunology, CD40 Ligand immunology, Pneumococcal Infections immunology
- Abstract
Streptococcus pneumoniae causes serious infections in children, the elderly, and immunocompromised patients. Protection against infections with S. pneumoniae is mediated through Abs against the capsular polysaccharides (caps-PS). We previously showed that the murine Ab response to caps-PS is dependent on CD40-CD40L interaction. In the present paper, we addressed the question of whether the CD40-CD40L-mediated modulation of the anti-caps-PS immune reaction is the result of a direct interaction between B lymphocytes and T lymphocytes or of an indirect interaction. SCID/SCID mice reconstituted with B lymphocytes from wild-type mice did not mount anti-caps-PS Abs. SCID/SCID mice reconstituted with B lymphocytes from wild-type mice and CD4+ T lymphocytes from wild-type mice but not CD4+ T lymphocytes from CD40L knockout mice stimulated the anti-caps-PS Ab response. This indicated that CD4+ T lymphocytes stimulated the anti-caps-PS Ab response in a CD40L-dependent manner. SCID/SCID mice reconstituted with B lymphocytes from CD40 knockout mice and CD4+ T lymphocytes from wild-type mice generated an anti-caps-PS Ab response that could be inhibited by MR1, a blocking anti-CD40L Ab. These data indicated that CD4+ T lymphocytes stimulated the anti-caps-PS Ab response in an indirect way. Finally, lethally irradiated CD40 knockout mice reconstituted with bone marrow from wild-type mice mounted an anti-caps-PS Ab response that was comparable to the Ab response in wild-type mice, revealing that the required CD40 was on hemopoietic cells. In conclusion, we provide evidence that CD4+ T lymphocytes expressing CD40L stimulate the Ab response to soluble caps-PS by interacting with CD40-expressing non-B cells.
- Published
- 2006
- Full Text
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46. Activation of antigen-presenting cells by DNA delivery vectors.
- Author
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Meng WS and Butterfield LH
- Subjects
- Animals, Biocompatible Materials pharmacology, Drug Carriers pharmacology, Humans, Lactic Acid pharmacology, Polyglycolic Acid pharmacology, Polylactic Acid-Polyglycolic Acid Copolymer, Polymers pharmacology, Virus Activation drug effects, Antigen-Presenting Cells drug effects, Antigen-Presenting Cells immunology, Antigen-Presenting Cells physiology, DNA administration & dosage, Dendritic Cells drug effects, Dendritic Cells immunology, Dendritic Cells physiology, Virus Activation genetics
- Abstract
Gene-based modulation of immune functions is a promising means of eliciting protective immunity and induction of tolerance. Novel viral and non-viral DNA delivery systems are being investigated to achieve efficient gene transfer into mammalian cells. Antigen-presenting cells (APCs), in particular dendritic cells, are crucial targets in this context due to their capacity to initiate and direct effector functions. The increasing relevance of APCs as targets of DNA vectors calls for an assessment of vector-driven activation of these cells. For viral vectors, a putative pathway of APC activation would be Toll-like receptor signalling for certain RNA genome viruses. On the other hand, non-viral vectors appear to mature APCs by interaction of polymeric particulates or bioactive lipids with cellular mechanisms. The rational design of DNA-based therapies is possible only when the intrinsic effects of the vector and immune modulation originating from the DNA are delineated. This paper will summarise recent reports of adjuvant properties of viral and non-viral delivery systems.
- Published
- 2005
- Full Text
- View/download PDF
47. The role of adjuvants in the development of mucosal vaccines.
- Author
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Vajdy M and Singh M
- Subjects
- Animals, Bacterial Toxins genetics, Bacterial Toxins immunology, Cholera Toxin genetics, Cholera Toxin immunology, Dendritic Cells immunology, Enterotoxins genetics, Enterotoxins immunology, Escherichia coli Proteins, Humans, Lipid A analogs & derivatives, Lipid A immunology, Liposomes, Mutation, Plant Lectins, Saponins, Vaccines immunology, Adjuvants, Immunologic administration & dosage, Antigen-Presenting Cells immunology, Immunity, Mucosal, Immunologic Memory, Vaccines administration & dosage
- Abstract
It is well-established that most pathogens that cause infectious diseases enter the host via mucosal membranes of the respiratory, digestive and genital tracts. Some parenterally administered vaccines induce protection against mucosal pathogens. However, there is increasing evidence that mucosal protection is better afforded by mucosal vaccination, particularly for the induction of memory responses. Mucosal vaccines must pass several difficult hurdles before entering the host and inducing an effective and protective immune response. This review deals with present and past efforts in devising effective mucosal vaccines using delivery systems and immunopotentiating adjuvants for protein-based vaccines. The paper will conclude with the authors' opinion on how the field will or should progress in the future and what will be the required components of ideal future mucosal vaccines that can induce immunological memory.
- Published
- 2005
- Full Text
- View/download PDF
48. Human airway epithelial cells present antigen to influenza virus-specific CD8+ CTL inefficiently after incubation with viral protein together with ISCOMATRIX.
- Author
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Rimmelzwaan GF, Boon AC, Geelhoed-Mieras MM, Voeten JT, Fouchier RA, and Osterhaus AD
- Subjects
- Adjuvants, Immunologic, Cell Line, Chromium Radioisotopes, Flow Cytometry, Gene Transfer Techniques, Genetic Vectors, HLA-A Antigens immunology, Humans, Immunity, Mucosal immunology, Interferon-gamma biosynthesis, Respiratory Mucosa cytology, Respiratory Mucosa immunology, Retroviridae genetics, Retroviridae immunology, Antigen-Presenting Cells immunology, CD8-Positive T-Lymphocytes immunology, Epithelial Cells immunology, Orthomyxoviridae immunology, T-Lymphocytes, Cytotoxic immunology, Viral Proteins immunology
- Abstract
In the present paper, an in vitro model was established in which the interaction between influenza virus-specific CD8+ T cells and human airway epithelial cells can be studied. To this end, the human lung epithelial cell line A549 was transduced with the HLA-A*0201 gene. This MHC class I allele is involved in the presentation of the immunodominant M158-66 cytotoxic T lymphocyte (CTL) epitope of the influenza A virus matrix protein. The A549-HLA-A2 cells and a CD8+ T cell clone specific for the M158-66 epitope were used to evaluate ISCOMATRIX (IMX), which is considered a potential mucosal adjuvant for influenza vaccines, for its capacity to activate virus-specific CTL after incubation with epithelial cells. It was found that virus infected epithelial cells activated virus-specific CTL efficiently. However, incubation of epithelial cells with ISCOMATRIX and recombinant M1 protein activated CD8+ T cells inefficiently, unlike the incubation of C1R cells expressing a HLA-A2 trans gene or HLA-A2+ B-lymphoblastoid cells with these reagents. It was concluded that this lack of antigen presentation by epithelial cells indicate that these cells are not subject to killing by virus-specific CTL upon instillation with ISCOMATRIX-based vaccines, which may be a favorable property of mucosal vaccines.
- Published
- 2004
- Full Text
- View/download PDF
49. Radiation-induced bystander effect in immune response.
- Author
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Liu SZ, Jin SZ, and Liu XD
- Subjects
- Animals, Antigen-Presenting Cells immunology, Antigen-Presenting Cells metabolism, Antigens, CD immunology, B7-1 Antigen immunology, B7-2 Antigen, Cell Division immunology, Cell Line, Coculture Techniques, Dose-Response Relationship, Radiation, Membrane Glycoproteins immunology, Mice, Nitric Oxide biosynthesis, Antigen-Presenting Cells radiation effects, Bystander Effect radiation effects, T-Lymphocytes immunology, X-Rays
- Abstract
Objective: Since most reports on bystander effect have been only concerned with radiation-induced damage, the present paper aimed at disclosing whether low dose radiation could induce a stimulatory or beneficial bystander effect., Methods: A co-culture system containing irradiated antigen presenting cells (J774A.1) and unirradiated T lymphocytes (EL-4) was established to observe the effect of J774A.1 cells exposed to both low and high doses of X-rays on the unirradiated EL-4 cells. Incorporation of 3H-TdR was used to assess the proliferation of the EL-4 cells, expression of CD80/86 and CD48 on J774A.1 cells was measured with immunohistochemistry and flow cytometry, respectively. NO release from J774A.1 cells was estimated with nitrate reduction method., Results: Low dose-irradiated J774A.1 cells could stimulate the proliferation of the unirradiated EL-4 cells while the high dose-irradiated J774A.1 cells exerted an inhibitory effect on the proliferation of the unirradiated EL-4 cells. Preliminary mechanistic studies illustrated that the differential changes in CD48 expression and NO production by the irradiated J774A.1 cells after high and low dose radiation might be important factors underlying the differential bystander effect elicited by different doses of radiation., Conclusion: Stimulatory bystander effect can be induced in immune cells by low dose radiation.
- Published
- 2004
50. Immunomodulatory effects of the HIV-1 gp120 protein on antigen presenting cells: implications for AIDS pathogenesis.
- Author
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Conti L, Fantuzzi L, Del Cornò M, Belardelli F, and Gessani S
- Subjects
- Acquired Immunodeficiency Syndrome immunology, Antigen-Presenting Cells immunology, HIV Envelope Protein gp120 immunology, HIV-1 immunology, Humans, Macrophages immunology, Protein Binding, Signal Transduction, Acquired Immunodeficiency Syndrome etiology, Antigen-Presenting Cells metabolism, HIV Envelope Protein gp120 metabolism, HIV-1 metabolism
- Abstract
Antigen presenting cell (APC) function is central to the development of an effective anti-viral immune response. Among APC, monocytes, macrophages and dendritic cells (DC) form the principal non-T cell compartment involved in in vivo HIV infection, and these cells play important and well-established roles in multiple aspects of viral pathogenesis. HIV infection may result in APC defects, which could ultimately contribute to the loss of CD4+ T cell responses observed early in HIV infection, when the CD4+ T cell number is still within the normal range. Extensive in vitro studies have demonstrated that the envelope glycoproteins of HIV-1 exert profound influences on various cell populations of the immune system, including hematopoietic progenitors, T and B lymphocytes, monocytes/ macrophages and DC, as well as on neuronal cells. The demonstration of the presence of envelope proteins both free in the circulation and bound to the surface of CD4+ cells suggests that gp120 interactions with non-infected cells can influence cellular functions in vivo, thus contributing to the immunopathogenesis of AIDS. This paper provides an overview of the present knowledge on gp120 binding, signal transduction triggering and interference with macrophage and DC functions and it highlights the importance of this interaction in the pathogenesis of AIDS.
- Published
- 2004
- Full Text
- View/download PDF
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