25 results
Search Results
2. Implications and Emerging Therapeutic Avenues of Inflammatory Response in HPV+ Head and Neck Squamous Cell Carcinoma.
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Castellano, Lúcio Roberto Cançado, Cruz, Sara Brito Silva Costa, Hier, Michael, Bonan, Paulo Rogério Ferreti, Alaoui-Jamali, Moulay A., and da Silva, Sabrina Daniela
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HEAD & neck cancer treatment , *CANCER patient psychology , *GENETIC mutation , *CANCER chemotherapy , *HEAD & neck cancer , *CELL physiology , *TREATMENT effectiveness , *PAPILLOMAVIRUS diseases , *QUALITY of life , *T cells , *CELL lines , *SQUAMOUS cell carcinoma , *COMORBIDITY , *DRUG resistance in cancer cells , *IMMUNOTHERAPY - Abstract
Simple Summary: Cancer in the head and neck region (HNSCC) is exponentially increasing due to human papillomavirus (HPV) infections. This paper helps us to understand the complexity of the inflammatory networks and the mechanisms of immune evasion in HPV+ HNSCC to open up new avenues and drive the discovery of useful tools to be translated clinically in the screening and treatment of these cases, especially to overcome resistance and improve patients' quality of life. Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignancies which have shown exponential incidence in the last two decades especially due to human papillomavirus (HPV) infection. The HPV family comprises more than 100 types of viruses with HPV16 and HPV18 being the most prevalent strains in HNSCC. Literature data reveal that the mutation profile as well as the response to chemotherapy and radiotherapy are distinct among HPV+ versus HPV-negative tumors. Furthermore, the presence of the virus induces activation of an immune response, in particular the recruitment of specific antiviral T lymphocytes to tumor sites. These T cells when activated produce soluble factors including cytokines and chemokines capable of modifying the local immune tumor microenvironment and impact on tumor response to the treatment. In this comprehensive review we investigated current knowledge on how the presence of an HPV can modify the inflammatory response systemically and within the tumor microenvironment's immunological responses, thereby impacting on disease prognosis and survival. We highlighted the research gaps and emerging approaches necessary to discover novel immunotherapeutic targets for HPV-associated HNSCC. [ABSTRACT FROM AUTHOR]
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- 2022
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3. Stenotrophomonas-maltophilia inhibits host cellular immunity by activating PD-1/PD-L1 signaling pathway to induce T-cell exhaustion.
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Wang, Min, Yin, Sheng, Qin, Qi, Peng, Yizhi, Hu, Zhengang, Zhu, Xiaolin, Liu, Lei, and Li, Xianping
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CELLULAR immunity , *T cells , *CELL morphology , *CELL membranes , *NOSOCOMIAL infections - Abstract
• We first described the S.maltophilia immunosuppressive effect on T cells and it is meaningful for immunosuppressed patients or co-infections. • T cells stimulated by S.maltophilia with CD4 and CD8 degraded via PD-1/PD-L1 pathway, which led to the massive apoptosis of T cells. • T cells were stimulated by S. maltophilia to secrete IFN-γ. Blocking the PD-1/PD-L1 pathway, apoptosis was suppressed. • S.maltophilia down-regulates host immunity by inhibiting immune cells. Smalotrophomonas maltophilia (S. maltophilia) is common in nosocomial infections. However, few studies have revealed the effect of S. maltophilia on cellular immunity in the host's immune system up to now. In clinical work, we accidentally discovered that S. maltophilia directly stimulated T cells to secrete IFN-γ. S. maltophilia was co-cultured with PBMCs to detect secretion of cytokines (IFN-γ, TNF-α and IL-2) and expression of cell surface molecules (CD3, CD4, CD8, CD69, CD147 and CD152) of T cells. We used light microscopy and electron microscopy to observe the cell morphology and subcellular structure of S. maltophilia co-cultured with lymphocytes. Flow cytometry and Western Blot were used to detect the expression of PD-1/PD-L1 and annexin V in cells. T cells stimulated by S. maltophilia secreted a large amount of IL-2, IFN-γ, and TNF-α. The expression of CD4 and CD8 on the cell surface were declined, accompanied by the activation of the PD-1/PD-L1 pathway, which eventually led to the massive apoptosis of T cells. Electron microscopy showed that cells showed significant apoptotic morphology. Blocking the PD-1/PD-L1 pathway can inhibit the apoptosis-inducing effect of S. maltophilia on T cells. These indicates that T cells are inhibited after being stimulated by S. maltophilia , and then accelerated to induce death without the initiation of an immunologic cascade. This paper demonstrates for the first time the inhibitory effect of S. maltophilia on cellular immunity, and the immunosuppressive effect induced by infection of S. maltophilia should be considered. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Altered thymic CD4+ T-cell recovery after allogeneic hematopoietic stem cell transplantation is critical for nocardiosis.
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Roussel, Xavier, Daguindau, Etienne, Berceanu, Ana, Desbrosses, Yohan, Saas, Philippe, Ferrand, Christophe, Seilles, Estelle, Pouthier, Fabienne, Deconinck, Eric, and Larosa, Fabrice
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HEMATOPOIETIC stem cell transplantation , *KILLER cells , *ALEMTUZUMAB , *ANTIBIOTIC prophylaxis , *NOCARDIOSIS , *T cells , *CELLULAR immunity - Abstract
Nocardia affects immunocompromised human host exhibiting an altered cell-mediated immunity. Infectious risk after allogeneic hematopoietic cell transplantation (AHCT) is significantly correlated to the recovery status of donor-derived immune system, especially CD4+ T-cells reconstitution and thymopoiesis. The purpose of this paper is to highlight a lack of cell-mediated immunity recovery for patients presenting a nocardiosis compared to a control cohort. This is a case control retrospective monocentric study. We retrospectively analyzed a monocentric cohort of 15 cases of nocardiosis after AHCT and we explored the degree of patients' immunosuppression by phenotyping circulating lymphoid subpopulations, including NK cells, CD8+ T-cells, CD4+ T-cells and CD19+ B-cells. We focused on CD4+ T-cell subsets to appreciate thymic output, especially on naive CD4+ T-cells (NTE, CD45RA+/RO− CD4+ T-cells) and recent thymic emigrants (RTE, CD4+CD45RA+/RO−/CD31+). Infected patients were paired with a control cohort of patients with identical transplantation characteristics screened on hematological disease, AHCT conditioning, primary graft- versus -host disease (GHVD) prophylaxis, graft type, sex, age, and season at the AHCT and data concerning immunological reconstitution were compared. At onset of nocardiosis, circulating lymphocytes and CD4+ T-cells means count were respectively 730/μL and 162/μL. CD8+ T-cells, CD56+ NK cells and CD19+ B-cells means count were respectively 362/μL, 160/μL, 112/μL. CD4+ T-cells subpopulations, naïve CD4+ T-cells production was impaired with NTE and RTE means count at 26/μL and 11/μL respectively. Comparison between nocardiosis cohort and control cohort over time highlight significant lower cellular count for lymphocytes, CD4+ T-cells, NTE and RTE with p = 0.001, p < 0.001, p < 0.001, p < 0.001 respectively. Immune recovery monitoring follow-up after AHCT is of particular importance to identify patients susceptible to develop Nocardiosis. Efficient microbiological investigations toward Nocardia such PCR should be used in case of compatible clinical presentation. [ABSTRACT FROM AUTHOR]
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- 2019
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5. Modelling the suppression of autoimmunity after pathogen infection.
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Oliveira, Bruno M. P. M., Trinchet, Ricard, Otero Espinar, María Victoria, Pinto, Alberto, and Burroughs, Nigel
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AUTOIMMUNITY , *PATHOGENIC microorganisms , *INTERLEUKIN-2 , *T cells , *CYTOKINES , *CELLULAR immunity - Abstract
We study a mathematical model of immune response by T cells where the regulatory T cells (Treg) inhibit interleukin 2 (IL‐2) secretion. We model the suppression of the autoimmune line of T cells after a different line of T cells responded to a pathogen infection. In this paper, we show that if the population of the pathogen responding line of T cells becomes large enough, the competition for IL‐2 and the increase in the death rates may lead to a depletion in the concentration of autoimmune T cells. Provided this lasts for a sufficiently long time, the concentration of autoimmune T cells can be brought down to values inside the basin of attraction of the controlled state, and autoimmunity can be suppressed. [ABSTRACT FROM AUTHOR]
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- 2018
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6. Immune repertoire: A potential biomarker and therapeutic for hepatocellular carcinoma.
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Han, Yingxin, Li, Hongmei, Guan, Yanfang, and Huang, Jian
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LIVER cancer , *BIOMARKERS , *CELLULAR immunity , *HIGH throughput screening (Drug development) , *IMMUNOSPECIFICITY , *CARCINOGENESIS , *TUMOR treatment , *ANIMALS , *B cells , *CELL receptors , *CELLULAR signal transduction , *IMMUNOLOGICAL adjuvants , *HEPATOCELLULAR carcinoma , *IMMUNOLOGY technique , *IMMUNOTHERAPY , *LIVER tumors , *T cells , *PHENOTYPES , *PREDICTIVE tests , *SEQUENCE analysis , *GENOTYPES , *DIAGNOSIS , *THERAPEUTICS - Abstract
The immune repertoire (IR) refers to the sum of B cells and T cells with functional diversity in the circulatory system of one individual at any given time. Immune cells, which reside within microenvironments and are responsible for protecting the human body, include T cells, B cells, macrophages, and dendritic cells. These dedicated immune cells have a characteristic structure and function. T and B cells are the main lymphocytes and are responsible for cellular immunity and humoral immunity, respectively. The T cell receptor (TCR) and B cell receptor (BCR) are composed of multiple peptide chains with antigen specificity. The amino acid composition and sequence order are more diverse in the complementarity-determining regions (including CDR1, CDR2 and CDR3) of each peptide chain, allowing a vast library of TCRs and BCRs. IR research is becoming increasingly focused on the study of CDR3 diversity. Deep profiling of CDR3s using high-throughput sequencing is a powerful approach for elucidating the composition and distribution of the CDR3s in a given sample, with in-depth information at the sequence level. Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. To identify novel biomarkers for diagnosis and drug targets for therapeutic interventions, several groups attempted to describe immune repertoire characteristics of the liver in the physiological environment or/and pathological conditions. This paper reviews the recent progress in IR research on human diseases, including hepatocellular carcinoma, attempting to depict the relationships between hepatocellular carcinogenesis and the IR, and discusses the possibility of IR as a potential biomarker and therapeutic for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Haralampos M. Moutsopoulos: A lifetime in autoimmunity
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Youinou, Pierre
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AUTOIMMUNITY , *SJOGREN'S syndrome , *T cells , *EPITHELIAL cells , *PEDIATRICS , *CELLULAR immunity , *MEDICAL care - Abstract
Abstract: Three years ago, the Journal of Autoimmunity and Autoimmunity Reviews launched a series of special issues devoted to the contributions of outstanding scholars in autoimmunology. The special issues are devoted not only to recognize achievements, but also to include a series of dedicated papers that reflect the scholar’s work, but also are cutting-edge research and reviews in immunology. This special issue is devoted to Haralampos M. Moutsopoulos of the National University of Athens. His contributions to patient care, teaching, and original research are legion. The papers that are included reflect not only a wide range of scholarship in autoimmunology, but importantly are written by his colleagues and friends, and by former students. They encompass original scholarship in Sjögren’s syndrome, but also in a number of effector pathways in both adult and pediatric autoimmunology. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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8. Mathematical analysis of a cell mediated immunity in a virus dynamics model with nonlinear infection rate and removal.
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Elaiw, A. M. and AlShamrani, N. H.
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IMMUNE response , *T cells , *NONLINEAR statistical models , *VIRUS diseases , *CELLULAR immunity , *LYAPUNOV functions - Abstract
In this paper, we investigate the dynamical behavior of a nonlinear model for viral infection with Cytotoxic T Lymphocyte (CTL) immune response. The model is a generalization of several models presented in the literature by considering more general functions for the: (i) intrinsic growth rate of uninfected cells; (ii) incidence rate of infection; (iii) natural death rate of infected cells; (iv) rate at which the infected cells are killed by CTL cells; (v) production and removal rates of viruses; (vi) activation and natural death rates of CTLs. We derive two threshold parameters R0 (the basic infection reproduction number) and R1 (the CTL immune response activation number) and establish a set of conditions on the general functions which are sufficient to determine the global dynamics of the model. By using suitable Lyapunov functions and LaSalle's invariance principle, we prove the global asymptotic stability of all equilibria of the model. [ABSTRACT FROM AUTHOR]
- Published
- 2016
9. The double-edge role of B cells in mediating antitumor T-cell immunity: Pharmacological strategies for cancer immunotherapy.
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Wang, Jing-Zhang, Zhang, Yu-Hua, Guo, Xin-Hua, Zhang, Hong-Yan, and Zhang, Yuan
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CANCER immunotherapy , *B cells , *ANTINEOPLASTIC agents , *T cells , *CELLULAR immunity , *CELL populations - Abstract
Emerging evidence reveals the controversial role of B cells in antitumor immunity, but the underlying mechanisms have to be explored. Three latest articles published in the issue 521 of Nature in 2015 reconfirmed the puzzling topic and put forward some explanations of how B cells regulate antitumor T-cell responses both positively and negatively. This paper attempts to demonstrate that different B-cell subpopulations have distinct immunological properties and that they are involved in either antitumor responses or immunosuppression. Recent studies supporting the positive and negative roles of B cells in tumor development were summarized comprehensively. Several specific B-cell subpopulations, such as IgG(+), IgA(+), IL-10(+), and regulatory B cells, were described in detail. The mechanisms underlying the controversial B-cell effects were mainly attributed to different B-cell subpopulations, different B-cell-derived cytokines, direct B cell-T cell interaction, different cancer categories, and different malignant stages, and the immunological interaction between B cells and T cells is mediated by dendritic cells. Promising B-cell-based antitumor strategies were proposed and novel B-cell regulators were summarized to present interesting therapeutic targets. Future investigations are needed to make sure that B-cell-based pharmacological strategies benefit cancer immunotherapy substantially. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Global analysis of a humoral and cellular immunity virus dynamics model with the Beddington-DeAngelis incidence rate.
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Su, Yongmei, Sun, Deshun, and Zhao, Lei
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GLOBAL analysis (Mathematics) , *CELLULAR immunity , *IMMUNE response , *T cells , *LYAPUNOV functions - Abstract
In this paper, a humoral and cellular immunity virus dynamics model with the Beddington-DeAngelis incidence rate is set up. We derive the basic reproductive number R0, the cytotoxic T lymphocytes immune response reproductive number R1, the humoral immune response reproductive number R2, humoral immune response competitive reproductive number R3, and cytotoxic T lymphocytes immune response competitive reproductive number R4, and a full description of the relation between the existence of the equilibria and reproductive numbers is given. The global properties of the five equilibria are obtained by constructing Lyapunov functions. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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- 2015
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11. Generation of antigen-specific cytotoxic T lymphocytes using a leukemic plasmacytoid dendritic cell line as antigen presenting cells
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Yamahira, Akie, Narita, Miwako, Nakamura, Takeshi, Watanabe, Norihiro, Kaji, Masami, Taniguchi, Tomoyo, Hashimoto, Shigeo, Furukawa, Tatsuo, Toba, Ken, Aizawa, Yoshifusa, Kuzushima, Kiyotaka, and Takahashi, Masuhiro
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T cells , *DENDRITIC cells , *LEUKEMIA , *CELLULAR immunity , *CYTOKINES , *CANCER immunotherapy , *ANTIGEN presenting cells , *CELLULAR therapy - Abstract
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 &y& Elsevier]
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- 2011
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12. Cytokine-Induced NK-Like T Cells: From Bench to Bedside.
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Yeh Ching Linn and Hui, Kam M.
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KILLER cells , *CYTOKINES , *IMMUNOREGULATION , *CELLULAR immunity , *T cells , *IMMUNOTHERAPY , *CLINICAL trials - Abstract
Cytokine-induced killer (CIK) cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations. [ABSTRACT FROM AUTHOR]
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- 2010
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13. Early T-cell activation biophysics.
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Henry, Nelly and Hivroz, Claire
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T cells , *MOLECULAR immune response , *MOLECULAR immunology , *IMMUNE system , *MAMMAL physiology , *CELLULAR immunity , *T-cell receptor genes , *CELLULAR control mechanisms , *FLUORESCENCE microscopy , *PHYSIOLOGY - Abstract
The T-cell is one of the main players in the mammalian immune response. It ensures antigen recognition at the surface of antigen-presenting cells in a complex and highly sensitive and specific process, in which the encounter of the T-cell receptor with the agonist peptide associated with the major histocompatibility complex triggers T-cell activation. While signaling pathways have been elucidated in increasing detail, the mechanism of TCR triggering remains highly controversial despite active research published in the past 10 years. In this paper, we present a short overview of pending questions on critical initial events associated with T-cell triggering. In particular, we examine biophysical approaches already in use, as well as future directions. We suggest that the most recent advances in fluorescence super-resolution imaging, coupled with the new classes of genetic fluorescent probes, will play an important role in elucidation of the T-cell triggering mechanism. Beyond this aspect, we predict that exploration of mechanical cues in the triggering process will provide new clues leading to clarification of the entire mechanism. [ [ABSTRACT FROM AUTHOR]
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- 2009
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14. Antimycobacterial immune responses in patients with pulmonary sarcoidosis.
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Hörster, Robert, Kirsten, Detlef, Gaede, Karoline Iris, Jafari, Claudia, Strassburg, Alan, Greinert, Ulf, Kalsdorf, Barbara, Ernst, Martin, and Lange, Christoph
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SARCOIDOSIS , *MYCOBACTERIUM tuberculosis , *CELLULAR immunity , *BRONCHOALVEOLAR lavage , *INTERFERONS , *DISEASE risk factors - Abstract
Sarcoidosis is a multisystem granulomatous disease of unknown origin. Pathogenetic involvement of Mycobacterium tuberculosis has frequently been discussed in the aetiology of sarcoidosis; however, studies still remain contradictory. We addressed the question of mycobacterial involvement in the pathogenesis of sarcoidosis by analysing cellular immune responses to mycobacterial antigens. We examined the interferon (IFN)-γ production by enzyme-linked immunospot in response to purified protein derivate (PPD) mycobacterial-specific antigen early secretory antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10 by peripheral blood mononuclear cells (PBMCs) and bronchoalveolar-lavage mononuclear cells (BALMCs) of patients with pulmonary sarcoidosis, smear-negative tuberculosis and controls. Release of IFN-γ in response to ex vivo contact with PPD, ESAT-6 or CFP-10 by BALMC and PBMC were comparable among patients with sarcoidosis and controls (PBMC P = 0.2326; BALMC P = 0.1767) and were less frequently observed in both groups compared to patients with tuberculosis (BALMC P < 0.05; PBMC P < 0.0001). Within PBMC, the immunophenotype of sarcoidosis patients differed from that of patients with tuberculosis, as well as from that of controls, while within BALMC it resembled that of patients with tuberculosis. In contrast to patients with tuberculosis, the frequency of mycobacteria-specific local and systemic immune responses is not elevated in patients with sarcoidosis when compared to controls. The immunophenotype represents the local resemblance of the granulomatous reaction underlying tuberculosis and sarcoidosis while showing systemical difference. These observations do not support a role of an infection with M. tuberculosis in the pathogenesis of sarcoidosis. Please cite this paper as: Hörster R, Kirsten D, Gaede KI, Jafari C, Strassburg A, Greinert U, Kalsdorf B, Ernst M and Lange C. Antimycobacterial immune responses in patients with pulmonary sarcoidosis. The Clinical Respiratory Journal 2009; 3: 229-238. [ABSTRACT FROM AUTHOR]
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- 2009
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15. B-cells get the T-cells but antibodies get the worms
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Pleass, Richard J. and Behnke, Jerzy M.
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CELLULAR immunity , *B cells , *T cells , *IMMUNOGLOBULINS , *NEMATODES , *ANIMAL models in research , *ANTIGEN presenting cells , *MEDICAL publishing , *IMMUNE response - Abstract
Two recent papers published in Immunity and Cell Host & Microbe underline the great importance of B cells and of antibodies (Abs) in orchestrating crucial T helper cell type 2 (Th2) protective immune responses to gastrointestinal nematodes. The findings in animal models now raise major questions as to how B cells and Abs carry out these functions in humans. Here we discuss recent technological advances in humanizing animal models at the level of both Abs and their Fc-receptors, that might provide some answers. [Copyright &y& Elsevier]
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- 2009
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16. Dietary fish oil increases the number of splenic macrophages secreting TNF-alpha and IL-10 but decreases the secretion of these cytokines by splenic T cells from mice.
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Petursdottir, Dagbjort H. and Hardardottir, Ingibjorg
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MACROPHAGES , *CYTOKINES , *ENZYME-linked immunosorbent assay , *IMMUNOREGULATION , *FISH oils , *MARINE animal oils , *CELLULAR immunity , *T cells , *BIOLOGICAL transport , *ANIMAL experimentation , *COMPARATIVE studies , *CORN oil , *FAT content of food , *INTERLEUKINS , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *PLANT proteins , *RESEARCH , *SPLEEN , *TUMOR necrosis factors , *EVALUATION research , *LIPOPOLYSACCHARIDES - Abstract
Dietary fish oil has immunomodulatory effects that are partly mediated by its effects on cytokine secretion. In this paper, we examine whether dietary fish oil has different effects on cytokine secretion by T cells and macrophages. Female BalbC mice were fed diets supplemented with 18% fish oil + 2% corn oil or 20% corn oil. Concanavalin A (ConA)- and LPS-induced TNF-alpha and IL-10 secretion by splenocytes was examined using ELISA. Dietary fish oil decreased ConA induced-, but increased LPS-induced, TNF-alpha and IL-10 secretion by total murine splenocytes. Dietary fish oil increased the number of splenocytes secreting TNF-alpha and IL-10, following stimulation with LPS, by 123 and 38%, respectively, but did not affect cytokine secretion by each cell, as determined using enzyme-linked immunospot. Spleens from mice fed the fish oil diet had over 2-fold higher proportion of macrophages with high expression of CD11b than spleens from mice fed the corn oil diet. In addition, fish oil increased the proportion of total and CD11b(+) splenocytes that expressed the LPS receptor complex molecules, CD14 and toll-like receptor (TLR)4/myeloid differentiation factor-2 (MD-2), by 85 and 28%, respectively. The increased proportion of macrophages expressing the LPS receptor complex molecules, CD14 and TLR4/MD-2, in spleens from mice fed the fish oil diet may explain the increased number of cells that secreted the cytokines after LPS stimulation. [ABSTRACT FROM AUTHOR]
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- 2007
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17. Novel synthesis of α-galactosyl-ceramides and confirmation of their powerful NKT cell agonist activity
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Lee, Adrianne, Farrand, Kathryn J., Dickgreber, Nina, Hayman, Colin M., Jürs, Stefan, Hermans, Ian F., and Painter, Gavin F.
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CELLS , *BIOLOGY , *T cells , *CELLULAR immunity - Abstract
Abstract: α-Galactosyl-ceramide (1) has been identified as a powerful modulator of immunological processes through its capacity to bind CD1d molecules and specifically activate invariant natural killer (NK)-like T cells (iNKT cells). This paper describes the synthesis of 1, the analogous α-galactosyl-ceramide 3, and its short chain analogue ‘OCH’ (2), by use of the 4,6-di-O-tert-butylsilylene (DTBS) protecting group to produce a powerful α-galactosylating agent. In vivo experiments confirmed these compounds to be potent and selective activators of iNKT cells in a CD1d-dependent manner, each inducing a unique profile of cytokine release. This synthesis strategy will permit the generation of novel derivatives for use in the study of the mechanism of iNKT cell activation. [Copyright &y& Elsevier]
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- 2006
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18. Biologic agents in psoriasis.
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Lee, Michael R. and Cooper, Alan J.
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T cells , *CYTOKINES , *CELLULAR immunity , *ETANERCEPT , *INFLIXIMAB , *ANTI-inflammatory agents - Abstract
This paper reviews the new biologic agents that selectively block the immunologic steps implicated in the pathogenesis of psoriasis. Four strategies have been targeted: reduction of the number of pathogenic T cells; inhibition of T-cell activation and migration; modulation of the immune system; and blockage of the activity of inflammatory cytokines. There are three classes: monoclonal antibodies, fusion proteins and recombinant cytokines or growth factors. The actions, efficacy and side-effect profile of the biologic agents, alefacept, efalizumab, etanercept and infliximab, are reviewed. [ABSTRACT FROM AUTHOR]
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- 2006
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19. Agent-based modeling of the context dependency in T cell recognition
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Casal, Arancha, Sumen, Cenk, Reddy, Timothy E., Alber, Mark S., and Lee, Peter P.
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T cells , *PEPTIDES , *MOLECULAR immune response , *CELLULAR immunity - Abstract
Abstract: Antigen recognition by T cells is a key event in the adaptive immune response. T cells scan the surface of antigen-presenting cells (APCs) or target cells for specific peptides bound to MHC molecules. In the physiological setting, a typical APC presents tens of thousands of diverse endogenous self-derived peptides complexed to MHC (pMHC complexes). When ‘foreign’ peptides are presented, they constitute a small fraction of the total surface peptide repertoire. As T cells seem to be capable of discerning minute amounts of ‘foreign’ peptides among a complex background of self-peptides, endogenous peptides are generally assumed to play no role in recognition. However, recent results suggest that these background peptides may alter the sensitivity of T cells to foreign peptides. Current experimental limitations preclude analysis of peptide mixtures approaching physiological complexity, making it difficult to further address the role of complex background peptides. In this paper, we present a computational model to test how complex, varied peptide populations on an APC could potentially modulate a T cell''s ability to detect the presence of small numbers of agonist peptides among a diverse population. We use the model to investigate the notion that under physiological conditions, T cell recognition of foreign peptides is context dependent, that is, T cells process signals gathered from all pMHC interactions, not just from a few agonist peptides while ignoring all others. [Copyright &y& Elsevier]
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- 2005
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20. IL-10 down-regulates costimulatory molecules onMycobacterium tuberculosis-pulsed macrophages and impairs the lytic activity of CD4 and CD8 CTL in tuberculosis patients.
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de la Barrera, S., Alem´n, M., Musella, R., Schierloh, P., Pasquinelli, V., García, V., Abbate, E., and del C.#Sasiain, M.
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LYMPHOCYTES , *MACROPHAGES , *MYCOBACTERIAL diseases , *LUNG diseases , *CELLULAR immunity , *T cells - Abstract
Activation of T cells requires both TCR-specific ligation and costimulation through accessory molecules during T cell priming. IFNγ is a key cytokine responsible for macrophage activation duringMycobacterium tuberculosis(Mtb) infection while IL-10 is associated with suppression of cell mediated immunity in intracellular infection. In this paper we evaluated the role of IFNγ and IL-10 on the function of cytotoxic T cells (CTL) and on the modulation of costimulatory molecules in healthy controls and patients with active tuberculosis (TB).γ-irradiated-Mtb(i-Mtb) induced IL-10 production from CD14+ cells from TB patients. Moreover, CD3+ T cells of patients with advanced disease also produced IL-10 after i-Mtbstimulation. In healthy donors, IL-10 decreased the lytic activity of CD4+ and CD8+ T cells whereas it increasedγδ-mediated cytotoxicity. Furthermore, we found that the presence of IL-10 induced a loss of the alternative processing pathways of antigen presentation along with a down-regulation of the expression of costimulatory molecule expression on monocytes and macrophages from healthy individuals. Conversely, neutralization of endogenous IL-10 or addition of IFNγ to either effector or target cells from TB patients induced a strong lytic activity mediated by CD8+ CTL together with an up-regulation of CD54 and CD86 expression on target cells. Moreover, we observed that macrophages from TB patients could use alternative pathways for i-Mtbpresentation. Taken together, our results demonstrate that the presence of IL-10 duringMtbinfection might contribute to mycobacteria persistence inside host macrophages through a mechanism that involved inhibition of MHC-restricted cytotoxicity against infected macrophages. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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21. Regulation of cytokine and chemokine transcription in a human TH2 type T-cell clone during the induction phase of anergy.
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O'Hehir, R. E., Lake, R. A., Schall, T. J., Yssel, H., Panagiotopoulou, E., and Lamb, J. R.
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CELLULAR immunity , *CYTOKINES , *LYMPHOCYTES , *IMMUNOREGULATION , *MESSENGER RNA , *IMMUNOLOGY , *IMMUNE response - Abstract
Background Selected cytokines produced by allergen specific CD4+ T cells from atopic individuals contribute to both the specific and non-specific effector mechanisms of the allergic immune response. The chemokine family of cytokines and tumour necrosis factor (TNF)-α are leucocyte regulatory and proinflammatory molecules. The chemokines include interleukin (IL)-8 and the RANTES/SIS cytokines. Objective There bas been no systematic survey of chemokine production in T-cell subtypes. Because of their wide range of biological properties, it might be expected that they would be closely regulated by T cells. This paper illustrates one way (through the characterization of T-cell clones) these questions might be addressed. Methods Northern blot analysis was used to quantitate steady state transcription of selected cytokine genes and enzyme linked immunosorbent assay (ELISA) was used to quantitate soluble product. Results mRNA expression of the chemokines (IL-8. HuMIP-lα and HuMIP-lβ) and TNFα is upregulated in TH2-like cloned house dust mite reactive human CD4+ T cells under conditions of activation and during the induction phase of anergy. Although the development of anergy superinduces mRNA for both IL-8 and TNFα, protein production is low compared with that released during activation. In contrast, RANTES, a chemoattractant for CD4+ /CD45RO+ memory T cells, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and anergy induction. The production of IL-2, IL-4 and IL-5 mRNA and proteins during the induction of anergy peaks at 2h after stimulation, whereas the kinetics following activation of the T cells is delayed in comparison. Conclusion These data show that the induction of the anergic state coincides with post-transcriptional regulation of selected cytokine genes. Further study of these phenomena will impact on our understanding of the mechanisms of induction of anergy and the regulation of allergic immune responses in desensitization. [ABSTRACT FROM AUTHOR]
- Published
- 1996
- Full Text
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22. A Fine Romance: T Follicular Helper Cells and B Cells
- Author
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King, Cecile
- Subjects
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T cells , *B cells , *IMMUNOGLOBULINS , *CELLULAR immunity , *IMMUNE response , *ANTIGENS - Abstract
T follicular helper (Tfh) cells help B cells to generate affinity-matured antibodies. Three papers in this issue of Immunity () provide information about the reciprocal relationship between B cells and Tfh cells. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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23. Go girls! Efficient female innate immunity.
- Author
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Howie, Sarah E. M.
- Subjects
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T cells , *CELLULAR immunity , *STREPTOCOCCAL diseases , *NATURAL immunity ,SEX differences (Biology) - Abstract
The author discusses a study which shows the sex differences in tissue resident immune cells. She notes that the paper indicates that the levels of resident T cells are twice as high compared to males. She says that the findings reveal the efficiency of female innate immunity in dealing with streptococcal infection.
- Published
- 2011
- Full Text
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24. Correction.
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T cells , *IMMUNOREGULATION , *CELLULAR immunity , *CELL culture - Abstract
The article presents corrections to several papers that were published in different issues of the journal "Proceedings of the National Academy of Sciences of the USA." One of the article "Glatiramer Acetate-Specific T Cells in the Brain Express T helper 2/3 Cytokines and Brain-Derived Neurotrophic Factor In Situ," by Rina Aharoni, Basak Kayhan, Raya Eilam, Michael Sela, and Ruth Arnon appeared in November 25, 2003 issue of the journal. Another article "Suppression of Myasthenogenic Responses of a T Cell Line by a Dual Altered Peptide Ligand by Induction of CD4 and CD25 Regulatory Cells," by Badiga Venkata Aruna, Michael Sela, and Edna Mozes appeared in the July 19, 2005 issue of the journal.
- Published
- 2005
- Full Text
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25. Research Snippets.
- Subjects
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DERMATOLOGY , *SKIN diseases , *SKIN inflammation , *ONCOGENIC viruses , *T cells , *CYTOKINES , *CELLULAR immunity - Abstract
This article presents information about current research in the field of dermatology. According to a research paper published in a 2004 issue of the "British Journal of Dermatology," envelope proteins of the human endogenous retroviruses family are expressed in human normal, psoriatic and atopic skin by immunostaining and western blotting and that their expressions are regulated by ultra violet irradiation. Another study published in a 2004 issue of the "British Journal of Dermatology," looked at which T cell attracting chemokines are involved in allergic contact dermatitis models in mice which differ in their cytokine expression profiles.
- Published
- 2004
- Full Text
- View/download PDF
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