title: Interleukin-6 is crucial for recall of influenza-specific memory CD4 T cells.
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.
authors.affiliation: Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Longhi
authors.forename: Kate
authors.initials: K
authors.lastname: Wright
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Lauder
authors.forename: Mari A
authors.initials: MA
authors.lastname: Nowell
authors.forename: Gareth W
authors.initials: GW
authors.lastname: Jones
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Godkin
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.forename: Awen M
authors.initials: AM
authors.lastname: Gallimore
mesh_terms: 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
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha