Type I IFN signaling facilitates the development of IL-10-producing effector CD8+ T cells during murine influenza virus infection.

Abstract

Recent evidence has suggested that IL‐10‐producing effector CD8+ T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL‐10‐producing effector CD8+ T cells are not completely defined. Here, we show that type I interferons (IFNs) are required for the development of IL‐10‐producing effector CD8+ T cells during influenza virus infection in mice. We find that type I IFNs can enhance IL‐27 production by lung APCs, thereby facilitating IL‐10‐producing CD8+ T‐cell development through a CD8+ T‐cell‐nonautonomous way. Surprisingly, we also demonstrate that direct type I IFN signaling in CD8+ T cells is required for the maximal generation of IL‐10‐producing CD8+ T cells. Type I IFN signaling in CD8+ T cells, in cooperation with IL‐27 and IL‐2 signaling, promotes and sustains the expression of IFN regulatory factor 4 (IRF4) and B‐lymphocyte‐induced maturation protein‐1 (Blimp‐1), two transcription factors required for the production of IL‐10 by effector CD8+ T cells. Our data reveal a critical role of the innate antiviral effector cytokines in regulating the production of a regulatory cytokine by effector CD8+ T cells during respiratory virus infection.