title: Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major.
abstract: CD4+ T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4+ T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4+ T cells simultaneously producing interferon-gamma, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-gamma. These data show that the quality of a CD4+ T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (TH1) cells.
authors.affiliation: Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, Maryland 20892, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Darrah
authors.forename: Dipti T
authors.initials: DT
authors.lastname: Patel
authors.forename: Paula M
authors.initials: PM
authors.lastname: De Luca
authors.forename: Ross W B
authors.initials: RW
authors.lastname: Lindsay
authors.forename: Dylan F
authors.initials: DF
authors.lastname: Davey
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Flynn
authors.forename: Søren T
authors.initials: ST
authors.lastname: Hoff
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Morris
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
mesh_terms: D000818:Animals; D006801:Humans; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D016052:Protozoan Vaccines / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D016052:Protozoan Vaccines