Publication details
Stability and function of regulatory T cells expressing the transcription factor T-bet
| Authors | |
|---|---|
| Year of publication | 2017 |
| Type | Article in Periodical |
| Magazine / Source | Nature |
| MU Faculty or unit | |
| Citation | |
| Web | https://www.nature.com/articles/nature22360 |
| Doi | http://dx.doi.org/10.1038/nature22360 |
| Keywords | ROR-GAMMA-T; DIFFERENTIATION; FOXP3; INFECTION; EFFECTOR; IMMUNITY; HOMEOSTASIS; GENERATION; GATA-3 |
| Description | 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 (T(H)1), T(H)2, and T(H)17) defined by expression of the key transcription factors T-bet, GATA3, and ROR gamma t, respectively(1). Regulatory T (T-reg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated T-reg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide T-reg cells with enhanced suppressive capacity(4-6). Whether expression of these factors in T-reg 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 T(H)1-associated transcription factor T-bet in mouse T-reg 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 T-reg cells-but not of T-bet expression in T-reg cells-resulted in severe T(H)1 autoimmunity. Conversely, following depletion of T-bet-T-reg cells, the remaining T-bet(+) cells specifically inhibited T(H)1 and CD8 T cell activation consistent with their co-localization with T-bet(+) effector T cells. These results suggest that T-bet(+) T-reg cells have an essential immunosuppressive function and indicate that T-reg cell functional heterogeneity is a critical feature of immunological tolerance. |