| First Author | Levine AG | Year | 2017 |
| Journal | Nature | Volume | 546 |
| Issue | 7658 | Pages | 421-425 |
| PubMed ID | 28607488 | Mgi Jnum | J:248943 |
| Mgi Id | MGI:6095426 | Doi | 10.1038/nature22360 |
| Citation | Levine AG, et al. (2017) Stability and function of regulatory T cells expressing the transcription factor T-bet. Nature 546(7658):421-425 |
| abstractText | 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 RORgammat, 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. |
