Staphylococcus aureus Infection of Mice Expands a Population of Memory γδ T Cells That Are Protective against Subsequent Infection
Staphylococcus aureus Infection of Mice Expands a Population of Memory γδ T Cells That Are Protective against Subsequent Infection
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DOI：
10.4049/jimmunol.1303420
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发表时间：
2014-04-15
影响因子：
4.4
通讯作者：
McLoughlin, Rachel M.
中科院分区：
文献类型：
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作者：
Murphy, Alison G.;O'Keeffe, Kate M.;McLoughlin, Rachel M.
金黄色葡萄球菌疫苗的开发在临床试验中一直失败，可能是由于诱导细胞免疫的效率低下。T细胞来源的IL-17是为数不多的已知与抗金黄色葡萄球菌免疫相关的因子之一，它通过促进吞噬细胞效应器功能来保护金黄色葡萄球菌免受感染。因此，全面了解离散的T细胞亚群对于部位特异性IL-17介导的细菌清除至关重要，这将为有效靶向细胞免疫的疫苗的开发提供信息。在这项研究中，我们已经确定了CD44(+)CD27(-)记忆γ-T细胞群体，该T细胞在感染金黄色葡萄球菌的C57BL/6小鼠时扩增，产生高水平的IL-17，并在再次感染该细菌时介导增强的细菌清除。这些细胞主要由V-Gamma 4(+)亚群组成，在最初的V-Gamma 1.1(+)和V-Gamma 2(+)T细胞应答后在感染部位蓄积。此外，这些V-Gamma 4(+)T细胞在细菌清除后长时间保留在腹膜和纵隔淋巴引流中。在初次感染期间，IL-1信号对于记忆中的γ-增量T细胞的激活和扩张是必不可少的，而在再次暴露于金黄色葡萄球菌时，IL-1信号对于记忆中的γ-增量T细胞的激活和扩张是必不可少的。我们的发现表明，与经典的α-βT细胞类似，暴露于金黄色葡萄球菌后可以诱导伽马-德尔塔T细胞的记忆反应，并提示诱导表达IL-17的伽玛-德尔塔T细胞可能是金黄色葡萄球菌保护性疫苗的重要特性。
The development of vaccines against Staphylococcus aureus has consistently failed in clinical trials, likely due to inefficient induction of cellular immunity. T cell-derived IL-17 is one of the few known correlates of antistaphylococcoal immunity, conferring protection against S. aureus infections through its ability to promote phagocytic cell effector functions. A comprehensive understanding of the discrete T cell subsets critical for site-specific IL-17-mediated bacterial clearance will therefore be necessary to inform the development of vaccines that efficiently target cellular immunity. In this study, we have identified a population of CD44(+)CD27(-) memory gamma delta T cells, expanded upon infection of C57BL/6 mice with S. aureus, which produce high levels of IL-17 and mediate enhanced bacterial clearance upon reinfection with the bacterium. These cells are comprised largely of the V gamma 4(+) subset and accumulate at the site of infection subsequent to an initial V gamma 1.1(+) and V gamma 2(+) T cell response. Moreover, these V gamma 4(+) T cells are retained in the peritoneum and draining mediastinal lymph nodes for a prolonged period following bacterial clearance. In contrast to its critical requirement for gamma delta T cell activation during the primary infection, IL-1 signaling was dispensable for activation and expansion of memory gamma delta T cells upon re-exposure to S. aureus. Our findings demonstrate that a gamma delta T cell memory response can be induced upon exposure to S. aureus, in a fashion analogous to that associated with classical alpha beta T cells, and suggest that induction of IL-17-expressing gamma delta T cells may be an important property of a protective vaccine against S. aureus.