Cytokine-Dependent Induction of CD4+ T cells with Cytotoxic Potential during Influenza Virus Infection

L Hua, S Yao, D Pham, L Jiang, J Wright… - Journal of …, 2013 - Am Soc Microbiol
L Hua, S Yao, D Pham, L Jiang, J Wright, D Sawant, AL Dent, TJ Braciale, MH Kaplan, J Sun
Journal of virology, 2013Am Soc Microbiol
Recent evidence has identified the role of granzyme B-and perforin-expressing CD4+ T cells
with cytotoxic potential in antiviral immunity. However, the in vivo cytokine cues and
downstream pathways governing the differentiation of these cells are unclear. Here, we
have identified that CD4+ T cells with cytotoxic potential are specifically induced at the site of
infection during influenza virus infection. The development of CD4+ T cells with cytotoxic
potential in vivo was dependent on the cooperation of the STAT2-dependent type I interferon …
Abstract
Recent evidence has identified the role of granzyme B- and perforin-expressing CD4+ T cells with cytotoxic potential in antiviral immunity. However, the in vivo cytokine cues and downstream pathways governing the differentiation of these cells are unclear. Here, we have identified that CD4+ T cells with cytotoxic potential are specifically induced at the site of infection during influenza virus infection. The development of CD4+ T cells with cytotoxic potential in vivo was dependent on the cooperation of the STAT2-dependent type I interferon signaling and the interleukin-2/interleukin-2 receptor alpha pathway for the induction of the transcription factors T-bet and Blimp-1. We showed that Blimp-1 promoted the binding of T-bet to the promoters of cytolytic genes in CD4+ T cells and was required for the cytolytic function of the in vitro- and in vivo-generated CD4+ T cells with cytotoxic potential. Thus, our data define the molecular basis of regulation of the in vivo development of this functionally cytotoxic Th subset during acute respiratory virus infection. The potential implications for the functions of these cells are discussed.
American Society for Microbiology