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

2017; Rockefeller University Press; Volume: 214; Issue: 3 Linguagem: Inglês

10.1084/jem.20161318

1540-9538

Andrew G. Levine, Saskia Hemmers, António P. Baptista, Michail Schizas, Mehlika B. Faire, Bruno Moltedo, Catherine Konopacki, Marc Schmidt‐Supprian, Ronald N. Germain, Piper M. Treuting, Alexander Y. Rudensky,

Immunotherapy and Immune Responses

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.