Signatures of T Cells as Correlates of Immunity to Francisella tularensis

PLoS One

Lawrence A. Wolfraim¹  Rafael Björk²  Monica Normark²  Anders Sjöstedt²  Cecilia Rietz²  Carl Zingmark²  Svenja Stöven²  Kjell Eneslätt² 

[1] DynPort Vaccine Company, A CSC Company, Frederick, Maryland, United States of America;Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå, Sweden

关键词: T cells;    Cytokines;    Francisella tularensis;    Immune response;    Cytotoxic T cells;    Cell-mediated immunity;    Vaccination and immunization;    Tularemia;   

DOI  :  10.1371/journal.pone.0032367

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY