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Molecular view of a beneficial T cell auto-reactivity---Auto-antigen mediated NKT cell activation.

机译:有益的T细胞自身反应性的分子视图-自体抗原介导的NKT细胞活化。

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摘要

The current dogma is that the immune system is meant to generate immune protection to pathogen and maintain tolerance to self. Auto-antigenic activation is mostly thought to be associated with auto-immune disease. NKT cells are innate-like T cells that recognize specific microbial antigens and also display autoreactivity to self antigens. Accumulated data suggest that auto-antigenic NKT cell activation is beneficial, however the mechanism remains poorly understood. We show here that auto-antigens serve as partial agonists for NKT cells activating comparatively normal ERK signaling but deficient calcium signaling. Auto-antigenic activation leads NKT cells to a specialized activation status. In this activated status, NKT cell cytokine production is biased to IL-13 and GM-CSF, which correlates the high histone acetylation basal level on those gene loci in NKT cell population; NKT cells are less sensitive to subsequent strong glycolipid antigen alpha-GalCer stimulation; and NKT cells are reversibly primed to promptly respond to subsequent innate danger signals such as IL-12 combined with IL-18. These results show that instead of pathogenesis, auto-antigenic activation of NKT cells is an essential part of physiological NKT cell function.
机译:当前的教条是免疫系统旨在对病原体产生免疫保护并维持对自身的耐受性。人们通常认为自身抗原激活与自身免疫性疾病有关。 NKT细胞是先天样T细胞,可识别特定的微生物抗原,并且还显示出对自身抗原的自身反应性。积累的数据表明自体抗原NKT细胞的激活是有益的,但是对该机制的了解仍然很少。我们在这里显示,自身抗原充当激活相对正常ERK信号但缺乏钙信号的NKT细胞的部分激动剂。自身抗原激活导致NKT细胞进入专门的激活状态。在这种激活状态下,NKT细胞的细胞因子产生偏向于IL-13和GM-CSF,这与NKT细胞群体中那些基因位点的高组蛋白乙酰化基础水平有关。 NKT细胞对随后的强糖脂抗原α-GalCer刺激较不敏感; NKT细胞和NKT细胞可逆地引发,以迅速响应随后的先天危险信号,例如IL-12与IL-18结合。这些结果表明,NKT细胞的自身抗原激活代替了发病机理,是生理性NKT细胞功能的重要组成部分。

著录项

  • 作者

    Wang, Xiaohua.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 111 p.
  • 总页数 111
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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