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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Human autoreactive CD4+ T cells from naive CD45RA+ and memory CD45RO+ subsets differ with respect to epitope specificity and functional antigen avidity.
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Human autoreactive CD4+ T cells from naive CD45RA+ and memory CD45RO+ subsets differ with respect to epitope specificity and functional antigen avidity.

机译：来自幼稚CD45RA +和记忆CD45RO +亚群的人自身反应性CD4 + T细胞在表位特异性和功能性抗原亲和力方面有所不同。

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摘要

T cells with specificity for self-Ags are normally present in the peripheral blood, and, upon activation, may target tissue Ags and become involved in the pathogenesis of autoimmune processes. In multiple sclerosis, a demyelinating disease of the CNS, it is postulated that inflammatory damage is initiated by CD4+ T cells reactive to myelin Ags. To investigate the potential naive vs memory origin of circulating myelin-reactive cells, we have generated myelin basic protein (MBP)- and tetanus toxoid-specific T cell clones from CD45RA+/RO- and CD45RO+/RA- CD4+ T cell subsets from the peripheral blood of multiple sclerosis patients and controls. Our results show that 1) the response to MBP, different from that to TT, predominantly emerges from the CD45RA+ subset; 2) the reactivity to immunodominant MBP epitopes mostly resides in the CD45RA+ subset; 3) in each individual, the recognition of single MBP epitopes is skewed to either subset, with no overlap in the Ag fine specificity; and 4) in spite of a lower expression of costimulatory and adhesion molecules, CD45RA+ subset-derived clones recognize epitopes with higher functional Ag avidity. These findings point to a central role of the naive CD45RA+ T cell subset as the source for immunodominant, potentially pathogenic effector CD4+ T cell responses in humans.
机译：对自身抗原具有特异性的T细胞通常存在于外周血中，一旦激活，就可以靶向组织抗原并参与自身免疫过程的发病机制。在多发性硬化症（一种中枢神经系统的脱髓鞘疾病）中，假定炎症损伤是由与髓磷脂Ags反应的CD4 + T细胞引发的。为了研究循环髓磷脂反应性细胞的潜在天真与记忆起源，我们从外周血CD45RA + / RO-和CD45RO + / RA-CD4 + T细胞亚群中产生了髓磷脂碱性蛋白（MBP）和破伤风类毒素特异性T细胞克隆多发性硬化症患者和对照组的血液。我们的结果表明：1）对MBP的响应不同于对TT的响应，主要来自CD45RA +亚群; 2）对免疫显性MBP表位的反应性主要存在于CD45RA +亚群中; 3）在每个个体中，单个MBP表位的识别偏向任一子集，且Ag细特异性没有重叠;和4）尽管共刺激分子和粘附分子的表达较低，但CD45RA +子集衍生的克隆仍能识别具有较高功能性Ag亲和力的表位。这些发现表明，幼稚的CD45RA + T细胞亚群作为人类免疫显性，潜在致病性效应器CD4 + T细胞反应的来源具有中心作用。

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