Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity.
Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity.
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DOI：
10.1084/jem.20161318
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发表时间：
2017-03-06
期刊：
影响因子：
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通讯作者：
Rudensky AY
中科院分区：
文献类型：
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作者：
Levine AG;Hemmers S;Baptista AP;Schizas M;Faire MB;Moltedo B;Konopacki C;Schmidt-Supprian M;Germain RN;Treuting PM;Rudensky AY
Levine等研究了具有单克隆T细胞受体（TCR）或随机TCR库的调节性T细胞代替其发育选择的特异性维持TCR依赖性基因表达和免疫抑制功能的程度。调节性T细胞（T reg细胞）T细胞受体（TCR）库是高度多样的，并偏向于识别自身抗原。T reg细胞的TCR表达是维持免疫耐受性和其特征性基因表达特征的主要部分所持续需要的;然而，这些过程需要何种程度的不同TCR介导的与同源自身抗原的相互作用仍然未知。在这项研究中，通过实验切换的T reg细胞TCR的剧目，以一个单一的T reg细胞TCR，我们证明，T reg细胞的功能和基因表达可以部分解耦TCR的多样性。T reg细胞TCR库向随机库的诱导转换也保留了抑制淋巴结病和T辅助细胞2型活化的能力，尽管程度有限。同时，T reg细胞TCR库的这些扰动导致显著的免疫细胞活化、组织炎症和最终严重的自身免疫，表明多样性和特异性对于最佳T reg细胞功能的重要性。
Levine et al. investigate the extent to which regulatory T cells with either a monoclonal T cell receptor (TCR) or random TCR repertoire in place of their developmentally selected specificities maintain TCR-dependent gene expression and immunosuppressive function. The regulatory T cell (T reg cell) T cell receptor (TCR) repertoire is highly diverse and skewed toward recognition of self-antigens. TCR expression by T reg cells is continuously required for maintenance of immune tolerance and for a major part of their characteristic gene expression signature; however, it remains unknown to what degree diverse TCR-mediated interactions with cognate self-antigens are required for these processes. In this study, by experimentally switching the T reg cell TCR repertoire to a single T reg cell TCR, we demonstrate that T reg cell function and gene expression can be partially uncoupled from TCR diversity. An induced switch of the T reg cell TCR repertoire to a random repertoire also preserved, albeit to a limited degree, the ability to suppress lymphadenopathy and T helper cell type 2 activation. At the same time, these perturbations of the T reg cell TCR repertoire led to marked immune cell activation, tissue inflammation, and an ultimately severe autoimmunity, indicating the importance of diversity and specificity for optimal T reg cell function.