IFN gamma-induction of T(H)1-like regulatory T cells controls antiviral responses

Regulatory T (T-reg) cells are an immunosuppressive population that are required to maintain peripheral tolerance and prevent tissue damage from immunopathology, via anti-inflammatory cytokines, inhibitor receptors and metabolic disruption. Here we show that T-reg cells acquire an effector-like state, yet remain stable and functional, when exposed to interferon gamma (IFN gamma) during infection with lymphocytic choriomeningitis and influenza A virus. T-reg cell-restricted deletion of the IFN gamma receptor (encoded by Ifngr1), but not the interleukin 12 (IL12) receptor (encoded by Il12rb2), prevented T(H)1-like polarization (decreased expression of T-bet, CXC motif chemokine receptor 3 and IFN gamma) and promoted T(H)2-like polarization (increased expression of GATA-3, CCR4 and IL4). T(H)1-like T-reg cells limited CD8(+) T cell effector function, proliferation and memory formation during acute and chronic infection. These findings provide fundamental insights into how T-reg cells sense inflammatory cues from the environment (such as IFN gamma) during viral infection to provide guidance to the effector immune response. This regulatory circuit prevents prolonged immunoinflammatory responses and shapes the quality and quantity of the memory T cell response. Here the authors show that unlike IL12, IFN gamma can induce a T helper 1-like state in regulatory T (T-reg) cells during viral infection in mice that suppresses effector T cell responses and memory formation.