14 results
Search Results
2. A novel immune dominance selection multi-objective optimization algorithm for solving multi-objective optimization problems.
- Author
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Xiao, Jin-ke, Li, Wei-min, Xiao, Xin-rong, and LV, Cheng-zhong
- Subjects
B cells ,T cells ,LYMPHOCYTES ,ANTIGENS ,ALGORITHMS - Abstract
In this paper, we propose a novel immune dominance selection multi-objective optimization algorithm (IDSMOA) to solve multi-objective numerical and engineering optimization problems in the real world. IDSMOA was inspired by the mechanism that controls how B cells and T cells differentiate, recombine, and mutate self-adjustably to produce new lymphocytes matching antigens with high affinity, then how lymphocytes cooperatively eliminate antigens. The main idea of IDSMOA is to promote 2 populations, population B and population T, to coevolve through an immune selection operator, immune clone operator, immune gen operator, and memory selection operator to produce satisfying Pareto front. Therefore, several operators enable IDSMOA to exploit and excavate the search space, and decrease the number of dominance resistant solutions (DRSs). We compared IDSMOA performance with 3 known multi-objective optimization algorithms and IDSMOA without the combination operator in simulation experiments optimizing 12 benchmark functions. Our simulations indicated that IDSMOA is a competitive optimization tool for multi-objective optimization problems. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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- View/download PDF
3. Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow.
- Author
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Siracusa, Francesco, McGrath, Mairi A., Maschmeyer, Patrick, Bardua, Markus, Lehmann, Katrin, Heinz, Gitta, Durek, Pawel, Heinrich, Frederik F., Mashreghi, Mir-Farzin, Hyun-Dong Chang, Radbruch, Andreas, and Koji Tokoyoda
- Subjects
BONE marrow ,T cells ,ANTIGENS ,B cells ,LYMPHOCYTES ,CYTOKINES ,PHENOTYPES - Abstract
The bone marrow maintains memory CD4 T cells, which provide memory to systemic antigens. Here we demonstrate that memory CD4 T cells are reactivated by antigen in the bone marrow. In a secondary immune response, antigen-specific T cells of the bone marrow mobilize and aggregate in immune clusters together with MHC class II-expressing cells, mostly B lymphocytes. They proliferate vigorously and express effector cytokines, but they do not develop into follicular T-helper cells. Neither do the B lymphocytes develop into germinal center B cells in the bone marrow. Within 10 days, the immune clusters disappear again. Within 30 days, the expanded antigen-specific memory CD4 T cells return to memory niches and are maintained again individually as resting cells. Thus, in secondary immune responses in the bone marrow T-cell memory is amplified, while in germinal center reactions of secondary lymphoid organs humoral memory is adapted by affinity maturation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
4. Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes.
- Author
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Worel, Nina, Frank, Nelli, Frech, Christian, and Fritsch, Gerhard
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CD34 antigen ,LYMPHOCYTES ,GRANULOCYTES ,COLONY-stimulating factors (Physiology) ,CANCER chemotherapy ,ANTIGEN analysis ,ANTIGENS ,BIOTHERAPY ,CELL differentiation ,COMBINATION drug therapy ,GRANULOCYTE-colony stimulating factor ,FLOW cytometry ,HETEROCYCLIC compounds ,T cells ,MEMBRANE glycoproteins ,LYMPHOCYTE subsets - Abstract
Background: Peripheral blood stem cells mobilized with granulocyte-colony-stimulating factor (G-CSF) with or without chemotherapy are routinely used for autologous hematopoietic cell transplantation. Plerixafor, a chemokine-receptor inhibitor, increases the amount of circulating CD34+ cells and improves harvest results. However, limited information is available regarding the composition of apheresis products with respect to CD34+ and lymphocyte subtypes collected after various mobilization regimens.Study Design and Methods: We used a recently established single-platform multicolor flow-cytometric analysis including CD45RA and CD133 to define CD34+ subpopulations and lymphocyte subsets in products obtained either after G-CSF with or without chemotherapy alone (G, n = 40) or with addition of plerixafor (GP, n = 40).Results: Absolute numbers of white blood cells and lymphocyte subtypes were significantly higher after plerixafor, which was not observed for absolute CD34+ counts. However, distinct differences in terms of CD34+ subtypes were observed. The most primitive multipotent progenitors (CD45RA-CD133+CD34+CD38low ) predominated significantly after G (median, 49.2%; range, 15.2%-63%) compared to GP (median, 34.4%; range, 12%-62%; p < 0.001), whereas more differentiated subsets clearly prevailed after GP.Conclusion: In contrast to the findings of other authors, our study shows a clear shift toward more committed CD34+ subsets after plerixafor in poor mobilizers and elucidates the importance of informative surface markers like CD45RA and CD133 in addition to CD38 to discriminate earlier from more committed CD34+ cells. Further studies are needed to analyze whether these findings have an impact on clinical outcome. [ABSTRACT FROM AUTHOR]- Published
- 2017
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- View/download PDF
5. Levels of hepatic Th17 cells and regulatory T cells upregulated by hepatic stellate cells in advanced HBV-related liver fibrosis.
- Author
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Xiaoyan Li, Yujie Su, Xuefeng Hua, Chan Xie, Jing Liu, Yuehua Huang, Liang Zhou, Min Zhang, Xu Li, Zhiliang Gao, Li, Xiaoyan, Su, Yujie, Hua, Xuefeng, Xie, Chan, Liu, Jing, Huang, Yuehua, Zhou, Liang, Zhang, Min, Li, Xu, and Gao, Zhiliang
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LIVER diseases ,FIBROSIS ,T helper cells ,KUPFFER cells ,HEPATITIS B virus ,PROTEIN metabolism ,HEPATITIS viruses ,ANTIGENS ,CELL receptors ,CELLS ,LIVER ,CIRRHOSIS of the liver ,LYMPHOCYTES ,T cells ,DINOPROSTONE ,DISEASE complications ,PHYSIOLOGY - Abstract
Background: Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive.Methods: Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University. Liver tissues at least 3 cm away from the tumor site were used for the analyses. Levels of Th17 cells and regulatory T cells were detected by flow cytometry analysis and immunohistochemistry. In vitro experiment, we adopted magnetic cell sorting to investigate how hepatic stellate cells regulate the levels of Th17 cells and regulatory T cells.Results: We found that hepatic Th17 cells and regulatory T cells were increased in patients with advanced stage HBV-related liver fibrosis. Hepatic stellate cells upregulated the levels of Th17 cells and regulatory T cells via PGE2/EP2 and EP4 pathway.Conclusions: We found that the increased levels of Th17 cells and regulatory T cells were upregulated by hepatic stellate cells. These results may provide insight into the role of hepatic stellate cells and Th17 cells and regulatory T cells in the persistence of fibrosis and into the occurrence of hepatocellular carcinoma following cirrhosis. [ABSTRACT FROM AUTHOR]- Published
- 2017
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6. Optimal Sequential Immunization Can Focus Antibody Responses against Diversity Loss and Distraction.
- Author
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Wang, Shenshen
- Subjects
IMMUNOGLOBULINS ,IMMUNOLOGIC memory ,ANTIGENS ,VACCINATION ,LYMPHOCYTES - Abstract
Affinity maturation is a Darwinian process in which B lymphocytes evolve potent antibodies to encountered antigens and generate immune memory. Highly mutable complex pathogens present an immense antigenic diversity that continues to challenge natural immunity and vaccine design. Induction of broadly neutralizing antibodies (bnAbs) against this diversity by vaccination likely requires multiple exposures to distinct but related antigen variants, and yet how affinity maturation advances under such complex stimulation remains poorly understood. To fill the gap, we present an in silico model of affinity maturation to examine two realistic new aspects pertinent to vaccine development: loss in B cell diversity across successive immunization periods against different variants, and the presence of distracting epitopes that entropically disfavor the evolution of bnAbs. We find these new factors, which introduce additional selection pressures and constraints, significantly influence antibody breadth development, in a way that depends crucially on the temporal pattern of immunization (or selection forces). Curiously, a less diverse B cell seed may even favor the expansion and dominance of cross-reactive clones, but only when conflicting selection forces are presented in series rather than in a mixture. Moreover, the level of frustration due to evolutionary conflict dictates the degree of distraction. We further describe how antigenic histories select evolutionary paths of B cell lineages and determine the predominant mode of antibody responses. Sequential immunization with mutationally distant variants is shown to robustly induce bnAbs that focus on conserved elements of the target epitope, by thwarting strain-specific and distracted lineages. An optimal range of antigen dose underlies a fine balance between efficient adaptation and persistent reaction. These findings provide mechanistic guides to aid in design of vaccine strategies against fast mutating pathogens. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
7. Allostimulatory Effects of Dendritic Cells with Characteristic Features of a Regulatory Phenotype.
- Author
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Kouwenberg, M., Jacobs, C. W. M., van der Vlag, J., and Hilbrands, L. B.
- Subjects
DENDRITIC cells ,PHENOTYPES ,TRANSPLANTATION of organs, tissues, etc. ,GENE expression ,GLYCOGEN synthase kinase-3 - Abstract
Introduction: Tolerogenic dendritic cells (DCs) have the potential to prolong graft survival after transplantation. Tolerogenic DCs are in general characterized by a low expression of co-stimulatory molecule and a high IL-10:IL-12 production ratio. Based on promising results with earlier used alternatively activated DCs, we aimed to generate in culture potentially tolerogenic DC by simultaneously blocking GSK3 by lithium chloride (LiCl) and stimulating TLR2 by PAM
3 CysSerLys4 . Materials and Methods: Bone marrow-derived LiClPAM3 DCs were generated by the addition of LiCl 24 hours before harvesting, and one hour later PAM3 CysSerLys4 . The phenotype of the DCs was assessed by determining the expression of co-stimulatory molecules in flow cytometry and cytokine production in ELISA, whereas their functional properties were tested in a mixed lymphocyte reaction. A fully MHC mismatched heterotopic heart transplant preceded by infusion of donor-derived LiClPAM3 DC was performed to assess the tolerogenic potential of LiClPAM3 DCs in vivo. Results: LiClPAM3 DCs displayed a tolerogenic phenotype accompanied with a low expression of co-stimulatory molecules and a high IL-10:IL-12 production ratio. However, in mixed lymphocyte reaction, LiClPAM3 DCs appeared superior in T cell stimulation, and induced Th1 and Th17 differentiation. Moreover, mice pretreated with LiClPAM3 DC displayed a reduced graft survival. Analysis of LiClPAM3 DC culture supernatant revealed high levels of CXCL-1, which was also found in supernatants of co-cultures of LiClPAM3 DC and T cells. Nevertheless, we could not show a role for CXCL-1 in T cell proliferation or activation in vitro. Discussion: LiClPAM3 DCs display in vitro a tolerogenic phenotype with a high IL-10:IL-12 ratio, but appeared to be highly immunogenic, since allograft rejection was accelerated. As yet unidentified LiClPAM3 DC-derived factors, may explain the immunogenic character of LiClPAM3 DCs in vivo. [ABSTRACT FROM AUTHOR]- Published
- 2016
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8. The re-emergence of antigen-specific tolerance as a potential therapy for MS.
- Author
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Steinman, Lawrence
- Subjects
MULTIPLE sclerosis ,T cells ,VIRUS diseases ,LYMPHOCYTES ,ANTIGENS - Abstract
Ideal therapy for inflammatory disease in the nervous system would preserve normal immune function, while suppressing only the pathologic immune responses that damage tissue and allowing for repair. In principle, antigen-specific therapy would eradicate unwanted adaptive immune responses—antibody and T-cell mediated—while preserving the integrity of other adaptive responses to infectious agents and retaining the ability to fight malignancy. However, at this time, for multiple sclerosis (MS) we do not have compelling evidence that would support any particular dominant immune response to any specific antigen or even a limited group of antigens. In fact, there are adaptive immune responses to a wide swathe of proteins and lipids found on neurons and myelin in MS. Unless controlling a few of the known immune responses is sufficient, antigen-specific therapy in MS may not have enough of an impact to modulate clinical outcome. However, in other neuroinflammatory conditions, such as neuromyelitis optica, the adaptive immune response is highly focused. Trials of antigen-specific therapy for neuroinflammatory disease might first be tested in diseases with a more limited adaptive immune response like neuromyelitis optica. The likelihood of a significant success for this therapeutic strategy might then ensue. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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9. Immune-mediated antitumor effect by type 2 diabetes drug, metformin.
- Author
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Shingo Eikawa, Mikako Nishida, Shusaku Mizukami, Chihiro Yamazaki, Eiichi Nakayama, and Heiichiro Udono
- Subjects
METFORMIN ,T cells ,LYMPHOCYTES ,ANTIGENS ,CYTOKINES - Abstract
Metformin, a prescribed drug for type 2 diabetes, has been reported to have anti-cancer effects; however, the underlying mechanism is poorly understood. Here we show that this mechanism may be immune-mediated. Metformin enabled normal but not T-cell-deficient SCID mice to reject solid tumors. In addition, it increased the number of CD8
+ tumor-infiltrating lymphocytes (TILs) and protected them from apoptosis and exhaustion characterized by decreased production of IL-2, TNFα, and IFNγ. CD8+ TILs capable of producing multiple cytokines were mainly PD-1- Tim-3+ , an effector memory subset responsible for tumor rejection. Combined use of metformin and cancer vaccine improved CD8+ TIL multifunctionality. The adoptive transfer of antigen-specific CD8+ T cells treated with metformin concentrations as low as 10 μM showed efficient migration into tumors while maintaining multifunctionality in a manner sensitive to the AMP-activated protein kinase (AMPK) inhibitor compound C. Therefore, a direct effect of metformin on CD8+ T cells is critical for protection against the inevitable functional exhaustion in the tumor microenvironment. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
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10. Profiling Immune Escape in Hodgkin's and Diffuse large B-Cell Lymphomas Using the Transcriptome and Immunostaining.
- Author
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Péricart, Sarah, Tosolini, Marie, Gravelle, Pauline, Rossi, Cédric, Traverse-Glehen, Alexandra, Amara, Nadia, Franchet, Camille, Martin, Elodie, Bezombes, Christine, Laurent, Guy, Brousset, Pierre, Fournié, Jean-Jacques, and Laurent, Camille
- Subjects
ANTIGENS ,CELL physiology ,COMPARATIVE studies ,B cell lymphoma ,IMMUNOHISTOCHEMISTRY ,LYMPHOCYTES ,HODGKIN'S disease ,MACROPHAGES ,STAINS & staining (Microscopy) ,SURVIVAL ,T cells ,MICROARRAY technology ,GENE expression profiling ,GENETICS ,DIAGNOSIS ,PROGNOSIS - Abstract
Therapeutic blockade of PD-1/PD-L1 shows promising results in Hodgkin's lymphoma (HL) and in some diffuse large B-cell lymphoma (DLBCL) patients, but biomarkers predicting such responses are still lacking. To this end, we recently developed a transcriptional scoring of immune escape (IE) in cancer biopsies. Using this method in DLBCL, we identified four stages of IE correlated with overall survival, but whether Hodgkin's lymphomas (HL) also display this partition was unknown. Thus, we explored the transcriptomic profiles of ~1000 HL and DLBCL using a comparative meta-analysis of their bulk microarrays. Relative to DLBCL, the HL co-clustered at the advanced stage of immune escape, displaying significant enrichment of both IE and T-cell activation genes. Analyses via transcriptome deconvolution and immunohistochemistry showed more CD3
+ and CD4+ tumor-infiltrating lymphocytes (TILs) in HL than DLBCL. Both HL and non-GCB DLBCL shared a high abundance of infiltrating CD8+ T-cells, but HL had less CD68+ CD163+ macrophages. The same cellular distribution of PD-1 and TIM-3 was observed in HL and DLBCL, though HL had more PD-L1 tumor cells and LAG-3 ME cells. This study illuminates the advanced stage of immune activation and escape in HL, consistent with the response to checkpoint blockade therapies for this type of lymphoma. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
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11. Commonality despite exceptional diversity in the baseline human antibody repertoire
- Author
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Briney, Bryan, Inderbitzin, Anne, Joyce, Collin, and Burton, Dennis R.
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Antibodies -- Analysis ,Human genome -- Analysis ,Human physiology -- Analysis ,Lymphocytes ,Genomics ,T cells ,Antigens ,Genes ,Immune system ,B cells ,Genetic research ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
In principle, humans can produce an antibody response to any non-self-antigen molecule in the appropriate context. This flexibility is achieved by the presence of a large repertoire of naive antibodies, the diversity of which is expanded by somatic hypermutation following antigen exposure.sup.1. The diversity of the naive antibody repertoire in humans is estimated to be at least 10.sup.12 unique antibodies.sup.2. Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 10.sup.9, the circulating B cell population samples only a small fraction of this diversity. Full-scale analyses of human antibody repertoires have been prohibitively difficult, primarily owing to their massive size. The amount of information encoded by all of the rearranged antibody and T cell receptor genes in one person--the 'genome' of the adaptive immune system--exceeds the size of the human genome by more than four orders of magnitude. Furthermore, because much of the B lymphocyte population is localized in organs or tissues that cannot be comprehensively sampled from living subjects, human repertoire studies have focused on circulating B cells.sup.3. Here we examine the circulating B cell populations of ten human subjects and present what is, to our knowledge, the largest single collection of adaptive immune receptor sequences described to date, comprising almost 3 billion antibody heavy-chain sequences. This dataset enables genetic study of the baseline human antibody repertoire at an unprecedented depth and granularity, which reveals largely unique repertoires for each individual studied, a subpopulation of universally shared antibody clonotypes, and an exceptional overall diversity of the antibody repertoire. A genetic study of the baseline human antibody repertoire, based on the circulating B cell populations of ten subjects, reveals universally shared antibody clonotypes within repertoires that are largely unique to the individual., Author(s): Bryan Briney [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] , Anne Inderbitzin [sup.1] [sup.6] , Collin Joyce [sup.1] [sup.2] [sup.3] [sup.4] , Dennis R. Burton [sup.1] [sup.2] [sup.4] [sup.5] [sup.7] Author [...]
- Published
- 2019
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12. Investigators at Hospitalet de Llobregat Zero in on Non-Small Cell Lung Cancer (Determinants of immunological evasion and immunocheckpoint inhibition response in non-small cell lung cancer: the genetic front)
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Cancer treatment ,Apoptosis ,Genetic research ,Physical fitness ,Small cell lung cancer -- Genetic aspects ,Non-small cell lung cancer -- Genetic aspects ,Biochemistry ,T cells ,Antigens ,Lymphocytes ,Anopheles ,Cell death ,Obesity ,Editors ,Lung cancer ,Health - Abstract
2019 JUL 20 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Researchers detail new data in Oncology - Non-Small Cell Lung Cancer. According [...]
- Published
- 2019
13. Investigators from University of Utrecht Target Personalized Medicine (Modular Core-shell Polymeric Nanoparticles Mimicking Viral Structures for Vaccination)
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Precision medicine ,Antigens ,Vaccination ,Pharmacogenomics ,T cells ,Nanoparticles ,Lymphocytes ,Communicable diseases ,Editors ,Health - Abstract
2019 JUN 5 (NewsRx) -- By a News Reporter-Staff News Editor at Vaccine Weekly -- Investigators publish new report on Drugs and Therapies - Personalized Medicine. According to news reporting [...]
- Published
- 2019
14. Investigators from Virginia Commonwealth University Zero in on Immunologic Receptors (A Dynamical Systems Perspective On Chimeric Antigen Receptor T-cell Dosing)
- Subjects
Antigens ,T cells ,Hematopoietic stem cell transplantation ,Motor vehicle driving ,Membrane proteins ,Cancer research ,Lymphocytes ,Surgery ,Immunologic factors ,Proteins ,Editors ,Biological sciences ,Health - Abstract
2019 APR 23 (NewsRx) -- By a News Reporter-Staff News Editor at Life Science Weekly -- A new study on Membrane Proteins - Immunologic Receptors is now available. According to [...]
- Published
- 2019
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