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Analyses of T cell repertoire in Theiler's virus infected mice.

机译：泰勒病毒感染小鼠的T细胞库分析。

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摘要

Intracerebral infection of Theiler's virus induces an immune-mediated demyleinating disease in susceptible mice, such as SJL mice, providing an excellent infection-induced animal model of human multiple sclerosis. In contrast, B6 mice are resistant to infection mainly due to strong virus-specific CD8+ T cell responses in the CNS. For this reason, T cell immune responses in B6 mice have been often compared to those in susceptible SJL mice to understand the nature of protective vs. pathogenic immunity. Therefore, first two chapters in this thesis, aimed to investigate and compare Vbeta repertoire of antigen-specific CD8+ T cells in resistant vs. susceptible mice. In the last chapter, we aimed to investigate CD4+ T cell responses since functional repertoire maturation of virus-specific CD4+ T cells during the TMEV infection is not studied well so far although oilgo-clonal expansion of virus-specific CD4+ T cells involved in disease progression of susceptible SJL mice. Hence, we developed TCR transgenic mice to investigate the functional status and the role of virus-specific CD4+ T cells in the CNS. We found that most of antigen-specific CD4+ T cells are predisposed to an antigen-unresponsive state in the CNS. However, the disease onset and progression of 69Tg (TCR transgenic mice in susceptible genetic background) mice were accelerated compared to those of 69B6.S (TCR transgenic mice in resistant genetic background) mice. Since these results are tightly correlated with higher number of Th17 cell infiltration in the CNS, Th17 cells may play an important role in the pathogenesis of susceptible mice.;In summary, from the data presented in this thesis, we hypothesize that strong CD8+ T cell responses do not necessarily have to be a result of broad spectrum of Vbeta family. In addition, although very few CD4+ T cells produce inflammatory cytokines like IL-17 and IFN-gamma, CD4+ T cells seem to be the key players in this disease model since they are sufficient to cause progressive demyelinating disease in the CNS. Therefore, this thesis gives important insights into to the CNS infiltrating virus-specific CD8+ and CD4+ T cell repertoire.
机译：泰勒病毒的脑内感染在易感小鼠（例如SJL小鼠）中诱发免疫介导的脱髓鞘疾病，从而为人类多发性硬化症提供了出色的感染诱导动物模型。相反，B6小鼠对感染具有抵抗力，这主要是由于CNS中强烈的病毒特异性CD8 + T细胞反应。因此，经常将B6小鼠中的T细胞免疫应答与易感性SJL小鼠中的T细胞免疫应答进行比较，以了解保护性免疫和致病性免疫的性质。因此，本论文的前两章旨在研究和比较抗性小鼠与易感小鼠中抗原特异性CD8 + T细胞的Vbeta库。在上一章中，我们旨在研究CD4 + T细胞的反应，因为到目前为止TMEV感染期间病毒特异性CD4 + T细胞的功能库成熟还没有得到很好的研究，尽管涉及疾病进展的病毒特异性CD4 + T细胞的油克隆扩增易感SJL小鼠。因此，我们开发了TCR转基因小鼠，以研究CNS中病毒特异性CD4 + T细胞的功能状态和作用。我们发现大多数抗原特异性CD4 + T细胞在CNS中易感抗原无反应状态。然而，与69B6.S（抗性遗传背景下的TCR转基因小鼠）相比，69Tg（易感遗传背景下的TCR转基因小鼠）小鼠的疾病发作和进展加快。由于这些结果与中枢神经系统中Th17细胞浸润的增加密切相关，因此Th17细胞可能在易感小鼠的发病机制中起重要作用。综上所述，根据本论文提供的数据，我们推测强CD8 + T细胞响应不一定是Vbeta家族广谱的结果。此外，尽管很少有CD4 + T细胞产生像IL-17和IFN-γ这样的炎性细胞因子，但CD4 + T细胞似乎是该疾病模型的关键参与者，因为它们足以引起中枢神经系统进行性脱髓鞘疾病。因此，本论文对中枢神经系统浸润病毒特异的CD8 +和CD4 + T细胞库提供了重要的见识。

著录项

  • 作者

    Kang, Hyun Seok.;

  • 作者单位

    Northwestern University.;

  • 授予单位 Northwestern University.;
  • 学科 Biology Virology.;Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 199 p.
  • 总页数 199
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:38:26

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