Kolata Julia B, Kühbandner Iris, Link Christopher, Normann Nicole, Vu Chi Hai, Steil Leif, Weidenmaier Christopher, Bröker Barbara M
Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald.
Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald.
J Infect Dis. 2015 Sep 1;212(5):830-8. doi: 10.1093/infdis/jiv128. Epub 2015 Mar 3.
Though Staphylococcus aureus is a major pathogen, vaccine trials have failed. In contrast, class-switched antibodies specific to S. aureus are common, implying immune memory formation and suggesting a large pool of S. aureus-reactive helper T-cells.
To elucidate the cellular arm of S. aureus-specific immune memory, the T-cell response in humans was characterized.
The proliferative response of human peripheral blood mononuclear cells (PBMCs) to S. aureus antigens and the frequency of S. aureus-specific T-cells were quantified by (3)H-thymidine incorporation; cytokine release was measured by flow cytometry.
Staphylococcus aureus particles and extracellular proteins elicited pronounced proliferation in PBMCs of healthy adults. This reflected a memory response with high frequencies of T-cells being activated by single S. aureus antigens. The whole S. aureus-specific T-cell pool was estimated to comprise 3.6% of T-cells with 35-fold differences between individuals (range, 0.2%-5.7%). When exposed to S. aureus antigens, the T-cells released predominantly but not solely T helper (Th)1/Th17 cytokines.
The large number of S. aureus antigen-reactive memory T-lymphocytes is likely to influence the course of S. aureus infection. To enable rational vaccine design, the naturally acquired human T-cell memory needs to be explored at high priority.
尽管金黄色葡萄球菌是一种主要病原体，但疫苗试验均告失败。相比之下，针对金黄色葡萄球菌的类别转换抗体很常见，这意味着免疫记忆的形成，并提示存在大量对金黄色葡萄球菌有反应的辅助性T细胞。
为阐明金黄色葡萄球菌特异性免疫记忆的细胞机制，对人类的T细胞反应进行了特征分析。
通过³H-胸腺嘧啶核苷掺入法对人外周血单个核细胞（PBMC）对金黄色葡萄球菌抗原的增殖反应及金黄色葡萄球菌特异性T细胞的频率进行定量；通过流式细胞术检测细胞因子释放情况。
金黄色葡萄球菌颗粒和细胞外蛋白可在健康成年人的PBMC中引发显著增殖。这反映了一种记忆反应，即单个金黄色葡萄球菌抗原可激活高频率的T细胞。据估计，整个金黄色葡萄球菌特异性T细胞库占T细胞的3.6%，个体之间存在35倍的差异（范围为0.2% - 5.7%）。当暴露于金黄色葡萄球菌抗原时，T细胞主要但并非仅释放辅助性T细胞1（Th1）/辅助性T细胞17（Th17）细胞因子。
大量对金黄色葡萄球菌抗原有反应的记忆性T淋巴细胞可能会影响金黄色葡萄球菌感染的进程。为实现合理的疫苗设计，亟需优先探索自然获得的人类T细胞记忆。
