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Signatures of T cells as correlates of immunity to Francisella tularensis.

Eneslätt K, Normark M, Björk R, Rietz C, Zingmark C, Wolfraim LA, Stöven S, Sjöstedt A - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå, Sweden.

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.

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Stimulation indices for the proliferative responses of human PBMC to recall stimulation with ffLVS for five days.Median values ± SEM per donor group of 12–16 individuals are shown. “pat” indicates convalescent tularemia patients, “vc” LVS vaccinees, and “nv” naïve individuals.
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pone-0032367-g001: Stimulation indices for the proliferative responses of human PBMC to recall stimulation with ffLVS for five days.Median values ± SEM per donor group of 12–16 individuals are shown. “pat” indicates convalescent tularemia patients, “vc” LVS vaccinees, and “nv” naïve individuals.

Mentions: Proliferative responses after recall stimulation of PBMC from immune donors, patients or vaccinees increased with increasing antigen concentrations and were significantly higher than those of cells from naïve individuals (Fig. 1, Table S1). PBMC samples from the majority of the immune donors were maximally induced by the medium antigen concentration of 0.1 cfu ffLVS/PBMC and no significant differences were observed between the two highest antigen concentrations for any of the donor groups. In addition, we did not find any significant differences between the two groups of immune donors for any antigen concentration or antigen-dependent increase (Table S1). The proliferative responses to the ffSCHU S4 were somewhat lower than those to the ffLVS antigen, but these differences were not statistically significant (not shown). In fact, the responses to the two antigens were correlated with a highly significant Spearman's correlation coefficient of >0.7.


Signatures of T cells as correlates of immunity to Francisella tularensis.

Eneslätt K, Normark M, Björk R, Rietz C, Zingmark C, Wolfraim LA, Stöven S, Sjöstedt A - PLoS ONE (2012)

Stimulation indices for the proliferative responses of human PBMC to recall stimulation with ffLVS for five days.Median values ± SEM per donor group of 12–16 individuals are shown. “pat” indicates convalescent tularemia patients, “vc” LVS vaccinees, and “nv” naïve individuals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3295757&req=5

pone-0032367-g001: Stimulation indices for the proliferative responses of human PBMC to recall stimulation with ffLVS for five days.Median values ± SEM per donor group of 12–16 individuals are shown. “pat” indicates convalescent tularemia patients, “vc” LVS vaccinees, and “nv” naïve individuals.
Mentions: Proliferative responses after recall stimulation of PBMC from immune donors, patients or vaccinees increased with increasing antigen concentrations and were significantly higher than those of cells from naïve individuals (Fig. 1, Table S1). PBMC samples from the majority of the immune donors were maximally induced by the medium antigen concentration of 0.1 cfu ffLVS/PBMC and no significant differences were observed between the two highest antigen concentrations for any of the donor groups. In addition, we did not find any significant differences between the two groups of immune donors for any antigen concentration or antigen-dependent increase (Table S1). The proliferative responses to the ffSCHU S4 were somewhat lower than those to the ffLVS antigen, but these differences were not statistically significant (not shown). In fact, the responses to the two antigens were correlated with a highly significant Spearman's correlation coefficient of >0.7.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå, Sweden.

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.

Show MeSH
Related in: MedlinePlus