IFNγ-induction of T H 1-like regulatory T cells controls antiviral responses.

Autor: Gocher-Demske AM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA., Cui J; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA., Szymczak-Workman AL; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Vignali KM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA., Latini JN; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA., Pieklo GP; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA., Kimball JC; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA., Avery L; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Program in Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA., Cipolla EM; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.; Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Huckestein BR; Program in Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.; Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Hedden L; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Meisel M; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Alcorn JF; Program in Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA., Kane LP; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Workman CJ; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA., Vignali DAA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. dvignali@pitt.edu.; Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. dvignali@pitt.edu.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. dvignali@pitt.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2023 May; Vol. 24 (5), pp. 841-854. Date of Electronic Publication: 2023 Mar 16.
DOI: 10.1038/s41590-023-01453-w
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
Externí odkaz: