Interleukin-6 Is Crucial for Recall of Influenza-Specific Memory CD4+ T Cells

PLoS Pathogens

Mari A. Nowell¹  Awen M. Gallimore¹  Simon A. Jones¹  Gareth W. Jones¹  Andrew J. Godkin¹  Kate Wright¹  Sarah N. Lauder¹  Maria Paula Longhi¹ 

[1] Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom

关键词: T cells;    Regulatory T cells;    Influenza viruses;    Memory T cells;    Cytotoxic T cells;    Influenza;    Antigen-presenting cells;    Spleen;   

DOI  :  10.1371/journal.ppat.1000006

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY