IFNγ-induction of TH1-like regulatory T cells controls antiviral responses

Autor: Angela M. Gocher-Demske, Jian Cui, Andrea L. Szymczak-Workman, Kate M. Vignali, Julianna N. Latini, Gwen P. Pieklo, Jesse C. Kimball, Lyndsay Avery, Ellyse M. Cipolla, Brydie R. Huckestein, Lee Hedden, Marlies Meisel, John F. Alcorn, Lawrence P. Kane, Creg J. Workman, Dario A. A. Vignali
Rok vydání: 2023
Předmět:
Zdroj: Nat Immunol
ISSN: 1529-2916
1529-2908
Popis: 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 (IFNγ) during infection with lymphocytic choriomeningitis and influenza A virus. T(reg) cell-restricted deletion of the IFNγ 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 IFNγ) 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 IFNγ) 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.
Databáze: OpenAIRE
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