Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity Journal Article
| Authors: | Levine, A. G.; Hemmers, S.; Baptista, A. P.; Schizas, M.; Faire, M. B.; Moltedo, B.; Konopacki, C.; Schmidt-Supprian, M.; Germain, R. N.; Treuting, P. M.; Rudensky, A. Y. |
| Article Title: | Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity |
| Abstract: | 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. © 2017 Levine et al. |
| Keywords: | lymph nodes; forkhead transcription factors; mouse; animal; animals; mice; physiology; t lymphocyte receptor; regulatory t lymphocyte; immunology; lymphocyte activation; receptors, antigen, t-cell; t-lymphocytes, regulatory; lymph node; t-cell antigen receptor specificity; autoimmunity; forkhead transcription factor; lymphocyte antigen receptor; foxp3 protein, mouse |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 214 |
| Issue: | 3 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2017-03-01 |
| Start Page: | 609 |
| End Page: | 622 |
| Language: | English |
| DOI: | 10.1084/jem.20161318 |
| PUBMED: | 28130403 |
| PROVIDER: | scopus |
| PMCID: | PMC5339675 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 September 2017 -- Source: Scopus |
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