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Publication : Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity.

First Author  Levine AG Year  2017
Journal  J Exp Med Volume  214
Issue  3 Pages  609-622
PubMed ID  28130403 Mgi Jnum  J:241076
Mgi Id  MGI:5897703 Doi  10.1084/jem.20161318
Citation  Levine AG, et al. (2017) Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity. J Exp Med 214(3):609-622
abstractText  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.
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