Physiological induction of regulatory Qa-1-restricted CD8+ T cells triggered by endogenous CD4+ T cell responses.
Physiological induction of regulatory Qa-1-restricted CD8+ T cells triggered by endogenous CD4+ T cell responses.
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DOI：
10.1371/journal.pone.0021628
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Nicoletti A
中科院分区：
文献类型：
--
作者：
Varthaman A;Clement M;Khallou-Laschet J;Fornasa G;Gaston AT;Dussiot M;Caligiuri G;Cantor H;Kaveri S;Nicoletti A
T细胞依赖性自身免疫性疾病的特征是识别靶抗原上免疫显性表位的T细胞克隆扩增。因此，对于给定的自身免疫性疾病，致病性T细胞克隆表达具有有限数量可变区域的T细胞受体，这些区域定义抗原特异性。Qa-1是一种MHC i类分子，从tcr的可变区向Qa-1限制性CD8+ T细胞提供肽。v ß-特异性CD8+ T细胞的诱导已被利用在一种称为“T细胞疫苗接种”（TCV）的免疫治疗策略中，该策略包括注射活化和减毒的CD4+ T细胞克隆，以诱导保护性CD8+ T细胞。我们假设，在没有外源性T细胞接种的情况下，qa -1限制性CD8+调节性T细胞也可能构成内源性CD4+ T细胞扩增时淋巴细胞反应的生理调节臂。我们用两种类型的抗原刺激免疫小鼠，以顺序扩增抗原特异性内源性CD4+ T细胞，这些细胞具有不同的抗原特异性，但其TCR中具有共同的Vß链。第一次免疫是用一种非自身抗原进行的，而第二次免疫是用一种髓磷脂衍生的肽进行的，这种肽已知会导致实验性自身免疫性脑脊髓炎（EAE），这是一种多发性硬化症小鼠模型。我们发现，在第一次内源性CD4+ T细胞反应中诱导的调节性v ß-特异性qa -1限制性CD8+ T细胞能够控制随后动员的致病性自身反应性CD4+ T细胞的扩增。综上所述，除了免疫治疗性TCV外，qa -1限制性特化CD8+调节性T细胞也可以在内源性CD4+ T细胞反应中诱导。与其他调节性T细胞亚群不同，这些qa -1限制性T细胞的作用似乎仅限于立即重新激活CD4+ T细胞。
T cell-dependent autoimmune diseases are characterized by the expansion of T cell clones that recognize immunodominant epitopes on the target antigen. As a consequence, for a given autoimmune disorder, pathogenic T cell clones express T cell receptors with a limited number of variable regions that define antigenic specificity. Qa-1, a MHC class I-like molecule, presents peptides from the variable region of TCRs to Qa-1-restricted CD8+ T cells. The induction of Vß-specific CD8+ T cells has been harnessed in an immunotherapeutic strategy known as the “T cell vaccination” (TCV) that comprises the injection of activated and attenuated CD4+ T cell clones so as to induce protective CD8+ T cells. We hypothesized that Qa-1-restricted CD8+ regulatory T cells could also constitute a physiologic regulatory arm of lymphocyte responses upon expansion of endogenous CD4+ T cells, in the absence of deliberate exogenous T cell vaccination. We immunized mice with two types of antigenic challenges in order to sequentially expand antigen-specific endogenous CD4+ T cells with distinct antigenic specificities but characterized by a common Vß chain in their TCR. The first immunization was performed with a non-self antigen while the second challenge was performed with a myelin-derived peptide known to drive experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. We show that regulatory Vß-specific Qa-1-restricted CD8+ T cells induced during the first endogenous CD4+ T cell responses are able to control the expansion of subsequently mobilized pathogenic autoreactive CD4+ T cells. In conclusion, apart from the immunotherapeutic TCV, Qa-1-restricted specialized CD8+ regulatory T cells can also be induced during endogenous CD4+ T cell responses. At variance with other regulatory T cell subsets, the action of these Qa-1-restricted T cells seems to be restricted to the immediate re-activation of CD4+ T cells.
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影响因子：
30.5
作者：
Reboldi, Andrea;Coisne, Caroline;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
4.4
作者：
Li, JF;Goldstein, I;Chess, L
通讯作者：
Chess, L
DOI：
10.1073/pnas.101123098
发表时间：
2001-05-22
影响因子：
11.1
作者：
Jiang, H;Braunstein, NS;Chess, L
通讯作者：
Chess, L
影响因子：
56.9
作者：
KOH, DR;FUNGLEUNG, WP;MAK, TW
通讯作者：
MAK, TW
影响因子：
15.9
作者：
Panoutsakopoulou, V;Huster, KM;Cantor, H
通讯作者：
Cantor, H