Title | Continuous requirement for the TCR in regulatory T cell function. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Levine AG, Arvey A, Jin W, Rudensky AY |
Journal | Nat Immunol |
Volume | 15 |
Issue | 11 |
Pagination | 1070-8 |
Date Published | 2014 Nov |
ISSN | 1529-2916 |
Keywords | Animals, Autoimmunity, Cell Adhesion, Cell Differentiation, Diphtheria Toxin, Female, Forkhead Transcription Factors, Hyaluronan Receptors, Immune Tolerance, Interferon-gamma, Interleukin-13, Interleukin-2, Interleukin-4, Ki-67 Antigen, Male, Mice, Receptors, Antigen, T-Cell, Receptors, Interleukin-2, Signal Transduction, T-Lymphocytes, Regulatory, Tamoxifen |
Abstract | Foxp3(+) regulatory T cells (T(reg) cells) maintain immunological tolerance, and their deficiency results in fatal multiorgan autoimmunity. Although heightened signaling via the T cell antigen receptor (TCR) is critical for the differentiation of T(reg) cells, the role of TCR signaling in T(reg) cell function remains largely unknown. Here we demonstrated that inducible ablation of the TCR resulted in T(reg) cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of T(reg) cell signature genes or altered ability to sense and consume interleukin 2 (IL-2). Instead, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated T(reg) cell transcriptional signature. Our results reveal a critical role for the TCR in the suppressor capacity of T(reg) cells. |
DOI | 10.1038/ni.3004 |
Alternate Journal | Nat. Immunol. |
PubMed ID | 25263123 |
PubMed Central ID | PMC4205268 |
Grant List | R37AI034206 / AI / NIAID NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R37 AI034206 / AI / NIAID NIH HHS / United States / / Howard Hughes Medical Institute / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:09pm