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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Levine, AG; Hemmers, S; Baptista, AP; Schizas, M; Faire, MB; Moltedo, B; Konopacki, C; Schmidt-Supprian, M; Germain, RN; Treuting, PM; Rudensky, AY

Published Date

  • March 6, 2017

Published In

Volume / Issue

  • 214 / 3

Start / End Page

  • 609 - 622

PubMed ID

  • 28130403

Pubmed Central ID

  • PMC5339675

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20161318

Language

  • eng

Conference Location

  • United States