title: Signatures of T cells as correlates of immunity to Francisella tularensis.
abstract: Tularemia or vaccination with the live vaccine strain (LVS) of Francisella tularensis confers long-lived cell-mediated immunity. We hypothesized that this immunity depends on polyfunctional memory T cells, i.e., CD4(+) and/or CD8(+) T cells with the capability to simultaneously express several functional markers. Multiparametric flow cytometry, measurement of secreted cytokines, and analysis of lymphocyte proliferation were used to characterize in vitro recall responses of peripheral blood mononuclear cells (PBMC) to killed F. tularensis antigens from the LVS or Schu S4 strains. PBMC responses were compared between individuals who had contracted tularemia, had been vaccinated, or had not been exposed to F. tularensis (naïve). Significant differences were detected between either of the immune donor groups and naïve individuals for secreted levels of IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, MCP-1, and MIP-1β. Expression of IFN-γ, MIP-1β, and CD107a by CD4(+)CD45RO(+) or CD8(+)CD45RO(+) T cells correlated to antigen concentrations. In particular, IFN-γ and MIP-1β strongly discriminated between immune and naïve individuals. Only one cytokine, IL-6, discriminated between the two groups of immune individuals. Notably, IL-2- or TNF-α-secretion was low. Our results identify functional signatures of T cells that may serve as correlates of immunity and protection against F. tularensis.
authors.affiliation: Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Eneslätt
authors.forename: Monica
authors.initials: M
authors.lastname: Normark
authors.forename: Rafael
authors.initials: R
authors.lastname: Björk
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rietz
authors.forename: Carl
authors.initials: C
authors.lastname: Zingmark
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Wolfraim
authors.forename: Svenja
authors.initials: S
authors.lastname: Stöven
authors.forename: Anders
authors.initials: A
authors.lastname: Sjöstedt
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D005604:Francisella tularensis / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014406:Tularemia / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D000939:Epitopes