Interleukin-6 is crucial for recall of influenza-specific memory CD4 T cells.
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.
Longhi
Maria Paula
MP
Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
Wright
Kate
K
Lauder
Sarah N
SN
Nowell
Mari A
MA
Jones
Gareth W
GW
Godkin
Andrew J
AJ
Jones
Simon A
SA
Gallimore
Awen M
AM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D015850:Interleukin-6 / Q000502:physiology*; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha