title: Helping themselves: optimal virus-specific CD4 T cell responses require help via CD4 T cell licensing of dendritic cells.
abstract: Although CD4(+) T cell help (Th) is critical for inducing optimal B cell and CD8(+) T cell responses, it remains unclear whether induction of CD4(+) Th responses postinfection are also dependent on CD4(+) T cell help. In this study, we show that activation of adoptively transferred Th cells during primary influenza A virus (IAV) infection enhances both the magnitude and functional breadth of endogenous primary IAV-specific CD4(+) T cell responses. This enhancement was dependent on CD154-CD40-dependent dendritic cell licensing and resulted in a greater recall capacity of IAV-specific CD4(+) and CD8(+) T memory responses after heterologous IAV infection. These data suggest that engaging pre-existing CD4 responses at the time of priming may be a strategy for improving cellular immunity after vaccination.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia;
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Olson
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia; and.
authors.forename: Shirley G K
authors.initials: SG
authors.lastname: Seah
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia;
authors.forename: Jolie
authors.initials: J
authors.lastname: Cullen
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia;
authors.forename: Marie
authors.initials: M
authors.lastname: Greyer
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia;
authors.forename: Kathryn
authors.initials: K
authors.lastname: Edenborough
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia;
authors.forename: Sammy
authors.initials: S
authors.lastname: Bedoui
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia; and.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia; sjturn@unimelb.edu.au.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D023201:CD40 Ligand