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首页> 外文学位 >The role of Fcgamma receptor III (CD16) in the regulation of gammadelta T cells in multiple sclerosis.
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The role of Fcgamma receptor III (CD16) in the regulation of gammadelta T cells in multiple sclerosis.

机译：Fcgamma受体III（CD16）在多发性硬化症中调节γT细胞的作用。

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摘要

Multiple Sclerosis (MS) is an autoimmune central nervous system (CNS) disease characterized by inflammatory infiltrates alongside demyelinated axons, axonal transections and degenerating neurons; the exact mechanism whereby the immune system causes disease is still unclear. This lab has been exploring the possibility that innate immune responses are involved in disease immunopathogenesis, in particular gammadelta T cells which are concentrated in MS lesions.;CD 16 is a low affinity Fcgamma receptor, an activation receptor for gammadelta T cells, and a mediator of cytotoxicity. In the first part of this study, I found that the number of CD16+ gammadelta T cells is elevated in MS patients compared with healthy controls. The increase is especially pronounced in patients with a progressive course, and the extent of this elevation shows a positive correlation with severity and duration. Secondly, two in vitro experimental systems were established to investigate the hypothesis that these CD16+ gammadelta T cells are capable of ADCC cytolysis. The results show that the cytotoxicity mediated by gammadelta T cells is significantly increased by the presence of a bridging antibody, and this effect could be abrogated by removal of Fc portion of antibody or by using CD16- effector cells, suggesting a CD16-specific antibody-mediated cytolytic contribution. This is the first study of its kind to confirm the ADCC capability of gammadelta T cells. Lastly, by using intracytoplasmic flow cytometry, I found that antibody-coated stimulant cells could induce production of cytokines from gammadelta T cells. Interestingly, the capability of producing Th2 cytokines exclusively resides in the CD16 + population, suggesting a regulative role of gammadelta T cells in the pathogenesis of MS.;The findings of this work tie together the innate and adaptive immune responses through an interaction that involves the stimulation of antibody production, possibly against CNS molecules such as myelin, via CD 16 expressing gammadelta T cells that could use these antibodies to enact a guided attack on CNS targets via the mechanism of ADCC. This study offers further novel insights into the possible roles of gammadelta T cells in MS that can involve both potentially pathogenic and immunoregulatory functions.;The work described in this thesis was undertaken to examine the possibility that gammadelta T cells, via their expression of CD16, mediate CNS injury by antibody dependent cell cytotoxicity (ADCC) and through the same encounter they release cytokines that regulate the immune responses.
机译：多发性硬化症（MS）是一种自身免疫性中枢神经系统（CNS）疾病，其特征是炎性浸润以及脱髓鞘的轴突，轴突横断和退化的神经元。免疫系统导致疾病的确切机制仍不清楚。该实验室一直在探索疾病免疫发病机制涉及先天免疫应答的可能性，特别是集中在MS病变中的伽玛三角洲T细胞。CD 16是一种低亲和力的Fcγ受体，伽玛三角洲T细胞的激活受体和一种介体。细胞毒性。在这项研究的第一部分中，我发现与健康对照组相比，MS患者中CD16 +γT细胞的数量有所增加。这种增加在进行性病程的患者中尤为明显，并且这种升高的程度与严重程度和持续时间呈正相关。其次，建立了两个体外实验系统以研究这些CD16 +γT细胞能够进行ADCC细胞裂解的假说。结果表明，存在桥联抗体可显着提高由γT细胞介导的细胞毒性，并且可以通过去除抗体的Fc部分或使用CD16效应细胞来消除这种效应，这表明CD16特异性抗体-介导的溶细胞作用。这是同类研究中首次确认γT细胞的ADCC能力的研究。最后，通过使用胞浆内流式细胞术，我发现抗体包被的刺激细胞可以诱导γδT细胞产生细胞因子。有趣的是，产生Th2细胞因子的能力仅存在于CD16 +群体中，这表明γδT细胞在MS的发病机理中具有调节作用。;这项工作的发现通过涉及以下方面的相互作用将先天性和适应性免疫反应联系在一起：通过表达CD 16的Gammadelta T细胞刺激抗体生产，可能针对诸如髓磷脂的CNS分子，这些细胞可以使用这些抗体通过ADCC的机制对CNS靶标进行引导性攻击。这项研究为伽玛三角洲T细胞在MS中可能涉及潜在的致病性和免疫调节功能的可能作用提供了新的见解。本论文中所述的工作旨在研究伽玛三角洲T细胞通过其CD16的表达，通过抗体依赖性细胞毒性（ADCC）介导CNS损伤，并且通过相同的相遇，它们释放调节免疫应答的细胞因子。

著录项

  • 作者

    Chen, Zhihong.;

  • 作者单位

    University of Ottawa (Canada).;

  • 授予单位 University of Ottawa (Canada).;
  • 学科 Biology Microbiology.;Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 189 p.
  • 总页数 189
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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