title: CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza.
abstract: We have outlined the carefully orchestrated process of CD4+ T-cell differentiation from naïve to effector and from effector to memory cells with a focus on how these processes can be studied in vivo in responses to pathogen infection. We emphasize that the regulatory factors that determine the quality and quantity of the effector and memory cells generated include (i) the antigen dose during the initial T-cell interaction with antigen-presenting cells; (ii) the dose and duration of repeated interactions; and (iii) the milieu of inflammatory and growth cytokines that responding CD4+ T cells encounter. We suggest that heterogeneity in these regulatory factors leads to the generation of a spectrum of effectors with different functional attributes. Furthermore, we suggest that it is the presence of effectors at different stages along a pathway of progressive linear differentiation that leads to a related spectrum of memory cells. Our studies particularly highlight the multifaceted roles of CD4+ effector and memory T cells in protective responses to influenza infection and support the concept that efficient priming of CD4+ T cells that react to shared influenza proteins could contribute greatly to vaccine strategies for influenza.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA. sswain@northnet.org
authors.forename: Susan L
authors.initials: SL
authors.lastname: Swain
authors.forename: Javed N
authors.initials: JN
authors.lastname: Agrewala
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Brown
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Jelley-Gibbs
authors.forename: Susanne
authors.initials: S
authors.lastname: Golech
authors.forename: Gail
authors.initials: G
authors.lastname: Huston
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jones
authors.forename: Cris
authors.initials: C
authors.lastname: Kamperschroer
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
authors.forename: K Kai
authors.initials: KK
authors.lastname: McKinstry
authors.forename: Eulogia
authors.initials: E
authors.lastname: Román
authors.forename: Tara
authors.initials: T
authors.lastname: Strutt
authors.forename: Nan-ping
authors.initials: NP
authors.lastname: Weng
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D009975:Orthomyxoviridae / Q000276:immunology*