title: Memory CD4+ T cells induce innate responses independently of pathogen.
abstract: Inflammation induced by recognition of pathogen-associated molecular patterns markedly affects subsequent adaptive responses. We asked whether the adaptive immune system can also affect the character and magnitude of innate inflammatory responses. We found that the response of memory, but not naive, CD4(+) T cells enhances production of multiple innate inflammatory cytokines and chemokines (IICs) in the lung and that, during influenza infection, this leads to early control of virus. Memory CD4(+) T cell-induced IICs and viral control require cognate antigen recognition and are optimal when memory cells are either T helper type 1 (T(H)1) or T(H)17 polarized but are independent of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) production and do not require activation of conserved pathogen recognition pathways. This represents a previously undescribed mechanism by which memory CD4(+) T cells induce an early innate response that enhances immune protection against pathogens.
authors.affiliation: Trudeau Institute, Saranac Lake, New York, USA. tms139@mail.usask.ca
authors.forename: Tara M
authors.initials: TM
authors.lastname: Strutt
authors.forename: K Kai
authors.initials: KK
authors.lastname: McKinstry
authors.forename: John P
authors.initials: JP
authors.lastname: Dibble
authors.forename: Caylin
authors.initials: C
authors.lastname: Winchell
authors.forename: Yi
authors.initials: Y
authors.lastname: Kuang
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Curtis
authors.forename: Gail
authors.initials: G
authors.lastname: Huston
authors.forename: Richard W
authors.initials: RW
authors.lastname: Dutton
authors.forename: Susan L
authors.initials: SL
authors.lastname: Swain
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D007113:Immunity, Innate; D007156:Immunologic Memory / Q000502:physiology; D009980:Influenza A virus / Q000472:pathogenicity*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma