Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå, Sweden.
PLoS One. 2012;7(3):e32367. doi: 10.1371/journal.pone.0032367. Epub 2012 Mar 6.
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.
土拉菌病或接种弗氏志贺菌活疫苗株（LVS）可产生长期的细胞介导免疫。我们假设这种免疫依赖于多功能记忆 T 细胞，即同时具有表达几种功能标记物能力的 CD4(+)和/或 CD8(+)T 细胞。多参数流式细胞术、细胞因子分泌测量和淋巴细胞增殖分析用于表征外周血单核细胞（PBMC）对 LVS 或 Schu S4 株杀死的弗氏志贺菌抗原的体外回忆反应。将 PBMC 反应与已感染土拉菌病、已接种疫苗或未接触弗氏志贺菌（未暴露）的个体进行比较。在分泌水平上，与未暴露个体相比，免疫供体组中的任何一组都检测到 IL-5、IL-6、IL-10、IL-12、IL-13、IFN-γ、MCP-1 和 MIP-1β 的差异。IFN-γ、MIP-1β 和 CD4(+)CD45RO(+)或 CD8(+)CD45RO(+)T 细胞的表达与抗原浓度相关。特别是，IFN-γ 和 MIP-1β 能很好地区分免疫和未暴露个体。只有一种细胞因子，IL-6，能区分两组免疫个体。值得注意的是，IL-2 或 TNF-α 的分泌水平较低。我们的结果确定了 T 细胞的功能特征，这些特征可能作为对弗氏志贺菌的免疫和保护的相关性。
