Stability and function of regulatory T cells expressing the transcription factor T-bet.

Journal Article (Journal Article)

Adaptive immune responses are tailored to different types of pathogens through differentiation of naive CD4 T cells into functionally distinct subsets of effector T cells (T helper 1 (TH1), TH2, and TH17) defined by expression of the key transcription factors T-bet, GATA3, and RORγt, respectively. Regulatory T (Treg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated Treg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide Treg cells with enhanced suppressive capacity. Whether expression of these factors in Treg cells-as in effector T cells-is indicative of heterogeneity of functionally discrete and stable differentiation states, or conversely may be readily reversible, is unknown. Here we demonstrate that expression of the TH1-associated transcription factor T-bet in mouse Treg cells, induced at steady state and following infection, gradually becomes highly stable even under non-permissive conditions. Loss of function or elimination of T-bet-expressing Treg cells-but not of T-bet expression in Treg cells-resulted in severe TH1 autoimmunity. Conversely, following depletion of T-bet- Treg cells, the remaining T-bet+ cells specifically inhibited TH1 and CD8 T cell activation consistent with their co-localization with T-bet+ effector T cells. These results suggest that T-bet+ Treg cells have an essential immunosuppressive function and indicate that Treg cell functional heterogeneity is a critical feature of immunological tolerance.

Full Text

Duke Authors

Cited Authors

  • Levine, AG; Mendoza, A; Hemmers, S; Moltedo, B; Niec, RE; Schizas, M; Hoyos, BE; Putintseva, EV; Chaudhry, A; Dikiy, S; Fujisawa, S; Chudakov, DM; Treuting, PM; Rudensky, AY

Published Date

  • June 15, 2017

Published In

Volume / Issue

  • 546 / 7658

Start / End Page

  • 421 - 425

PubMed ID

  • 28607488

Pubmed Central ID

  • PMC5482236

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature22360


  • eng

Conference Location

  • England