title: Direct IL-6 Signals Maximize Protective Secondary CD4 T Cell Responses against Influenza.
abstract: Memory T cells can often respond against pathogens that have evaded neutralizing Abs and are thus key to vaccine-induced protection, yet the signals needed to optimize their responses are unclear. In this study, we identify a dramatic and selective requirement for IL-6 to achieve optimal memory CD4 T cell recall following heterosubtypic influenza A virus (IAV) challenge of mice primed previously with wild-type or attenuated IAV strains. Through analysis of endogenous T cell responses and adoptive transfer of IAV-specific memory T cell populations, we find that without IL-6, CD4+, but not CD8+, secondary effector populations expand less and have blunted function and antiviral impact. Early and direct IL-6 signals to memory CD4 T cells are required to program maximal secondary effector responses at the site of infection during heterosubtypic challenge, indicating a novel role for a costimulatory cytokine in recall responses.
authors.affiliation: Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827; tara.strutt@ucf.edu kai.mckinstry@ucf.edu.|Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605; and.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Strutt
authors.affiliation: Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827; tara.strutt@ucf.edu kai.mckinstry@ucf.edu.|Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605; and.
authors.forename: Karl Kai
authors.initials: KK
authors.lastname: McKinstry
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605; and.
authors.forename: Yi
authors.identifier: 0000-0002-3266-1781
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Finn
authors.affiliation: Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827.
authors.forename: Kunal
authors.initials: K
authors.lastname: Dhume
authors.affiliation: Wadsworth Center, Albany, NY 12201.
authors.forename: Stewart
authors.initials: S
authors.lastname: Sell
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605; and.
authors.forename: Susan L
authors.identifier: 0000-0002-3643-8018
authors.initials: SL
authors.lastname: Swain
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D015850:Interleukin-6 / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D015850:Interleukin-6