Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
Eur J Immunol. 2011 Apr;41(4):974-80. doi: 10.1002/eji.201040923. Epub 2011 Feb 21.
The efficacy of many vaccines against intracellular bacteria depends on the generation of cell-mediated immunity, but studies to determine the duration of immunity are usually confounded by re-exposure. The causative agent of tularemia, Francisella tularensis, is rare in most areas and, therefore, tularemia vaccination is an interesting model for studies of the longevity of vaccine-induced cell-mediated immunity. Here, lymphocyte proliferation and cytokine production in response to F. tularensis were assayed in two groups of 16 individuals, vaccinated 1-3 or 27-34 years previously. As compared to naïve individuals, vaccinees of both groups showed higher proliferative responses and, out of 17 cytokines assayed, higher levels of MIP-1β, IFN-γ, IL-10, and IL-5 in response to recall stimulation. The responses were very similar in the two groups of vaccinees. A statistical model was developed to predict the immune status of the individuals and by use of two parameters, proliferative responses and levels of IFN-γ, 91.1% of the individuals were correctly classified. Using flow cytometry analysis, we demonstrated that during recall stimulation, expression of IFN-γ by CD4(+) CCR7(+) , CD4(+) CD62L(+) , CD8(+) CCR7(+) , and CD8(+) CD62L(+) cells significantly increased in samples from vaccinated donors. In conclusion, cell-mediated immunity was found to persist three decades after tularemia vaccination without evidence of decline.
许多针对细胞内细菌的疫苗的功效依赖于细胞介导免疫的产生，但确定免疫持久性的研究通常因再次暴露而受到干扰。土拉弗朗西斯菌是土拉热的病原体，在大多数地区很少见，因此，土拉热疫苗接种是研究疫苗诱导的细胞介导免疫持久性的一个有趣模型。在此，我们在两组 16 名个体中检测了对 F. tularensis 的淋巴细胞增殖和细胞因子产生，这两组个体分别在 1-3 年前和 27-34 年前接种了疫苗。与未接触过的个体相比，两组疫苗接种者的增殖反应均较高，在检测的 17 种细胞因子中，MIP-1β、IFN-γ、IL-10 和 IL-5 的水平也更高。两组疫苗接种者的反应非常相似。我们建立了一个统计模型来预测个体的免疫状态，通过使用两个参数，增殖反应和 IFN-γ 水平，91.1%的个体被正确分类。通过流式细胞术分析，我们证明在回忆刺激期间，来自疫苗接种供体的样本中 CD4(+) CCR7(+)、CD4(+) CD62L(+)、CD8(+) CCR7(+)和 CD8(+) CD62L(+)细胞中 IFN-γ的表达显著增加。总之，在没有证据表明下降的情况下，细胞介导免疫在接种土拉热疫苗 30 年后仍被发现持续存在。
