Interleukin-6 is crucial for recall of influenza-specific memory CD4 T cells |
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Authors: | Longhi Maria Paula Wright Kate Lauder Sarah N Nowell Mari A Jones Gareth W Godkin Andrew J Jones Simon A Gallimore Awen M |
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Institution: | Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom;Mount Sinai School of Medicine, United States of America |
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Abstract: | Currently, our understanding of mechanisms underlying cell-mediated immunity and particularly of mechanisms that promote robust T cell memory to respiratory viruses is incomplete. Interleukin (IL)-6 has recently re-emerged as an important regulator of T cell proliferation and survival. Since IL-6 is abundant following infection with influenza virus, we analyzed virus-specific T cell activity in both wild type and IL-6 deficient mice. Studies outlined herein highlight a novel role for IL-6 in the development of T cell memory to influenza virus. Specifically, we find that CD4+ but not CD8+ T cell memory is critically dependent upon IL-6. This effect of IL-6 includes its ability to suppress CD4+CD25+ regulatory T cells (Treg). We demonstrate that influenza-induced IL-6 limits the activity of virus-specific Tregs, thereby facilitating the activity of virus-specific memory CD4+ T cells. These experiments reveal a critical role for IL-6 in ensuring, within the timeframe of an acute infection with a cytopathic virus, that antigen-specific Tregs have no opportunity to down-modulate the immune response, thereby favoring pathogen clearance and survival of the host. |
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