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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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Related in: MedlinePlus

Levels of cytokines secreted by human PBMC after recall stimulation with ffLVS or ffSchu S4 for five days.Cytokine concentrations were measured in cell culture supernatants using multiplex analysis. Median values ± SEM from PBMC samples of 14–16 individuals per donor group are shown (black bars indicate convalescent patients; grey bars indicate LVS vaccinees; white bars indicate naïve donors). Statistically significant differences between immune and naïve donors are marked by asterisks (P<0.05).
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pone-0032367-g003: Levels of cytokines secreted by human PBMC after recall stimulation with ffLVS or ffSchu S4 for five days.Cytokine concentrations were measured in cell culture supernatants using multiplex analysis. Median values ± SEM from PBMC samples of 14–16 individuals per donor group are shown (black bars indicate convalescent patients; grey bars indicate LVS vaccinees; white bars indicate naïve donors). Statistically significant differences between immune and naïve donors are marked by asterisks (P<0.05).

Mentions: Previously, we found that PBMC from LVS vaccinated individuals secreted higher amounts of 11 cytokines in response to recall stimulation with ffLVS than did PBMC from naïve individuals, although only IL-5, IL-10, IFN-γ, and MIP-1β were significantly higher [7]. Most of these cytokines had also been shown to be expressed during F. tularensis-immune responses in a mouse model [18]. Therefore, we analyzed secretion of the same cytokines. Statistically significant differences between either of the immune donor groups and naïve individuals were consistently detected for eight out of the eleven cytokines, i.e., IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, MCP-1, and MIP-1β, and their secretion increased with increasing antigen concentrations (Figs. 2 and 3, Table S2). Surprisingly, this was not true for IL-2 and only partly true for TNF-α. Only IL-6 differed between the two groups of immune donors. Curiously, in the absence of antigen, there were somewhat higher levels of MIP-1β in PBMC cultures from immune donors than in those from naïve donors.


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)

Levels of cytokines secreted by human PBMC after recall stimulation with ffLVS or ffSchu S4 for five days.Cytokine concentrations were measured in cell culture supernatants using multiplex analysis. Median values ± SEM from PBMC samples of 14–16 individuals per donor group are shown (black bars indicate convalescent patients; grey bars indicate LVS vaccinees; white bars indicate naïve donors). Statistically significant differences between immune and naïve donors are marked by asterisks (P<0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0032367-g003: Levels of cytokines secreted by human PBMC after recall stimulation with ffLVS or ffSchu S4 for five days.Cytokine concentrations were measured in cell culture supernatants using multiplex analysis. Median values ± SEM from PBMC samples of 14–16 individuals per donor group are shown (black bars indicate convalescent patients; grey bars indicate LVS vaccinees; white bars indicate naïve donors). Statistically significant differences between immune and naïve donors are marked by asterisks (P<0.05).
Mentions: Previously, we found that PBMC from LVS vaccinated individuals secreted higher amounts of 11 cytokines in response to recall stimulation with ffLVS than did PBMC from naïve individuals, although only IL-5, IL-10, IFN-γ, and MIP-1β were significantly higher [7]. Most of these cytokines had also been shown to be expressed during F. tularensis-immune responses in a mouse model [18]. Therefore, we analyzed secretion of the same cytokines. Statistically significant differences between either of the immune donor groups and naïve individuals were consistently detected for eight out of the eleven cytokines, i.e., IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, MCP-1, and MIP-1β, and their secretion increased with increasing antigen concentrations (Figs. 2 and 3, Table S2). Surprisingly, this was not true for IL-2 and only partly true for TNF-α. Only IL-6 differed between the two groups of immune donors. Curiously, in the absence of antigen, there were somewhat higher levels of MIP-1β in PBMC cultures from immune donors than in those from naïve donors.

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