Granuloma formation is a form of delayed-type hypersensitivity requiring CD4(+) T cells. Granulomas control the growth and dissemination of pathogens, preventing host inflammation from harming surrounding tissues. Using a murine model of Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) infection we studied the extent of T cell heterogeneity present in liver granulomas. We demonstrate that the TCR repertoire of granuloma-infiltrating T cells is very diverse even at the single-granuloma level, suggesting that before granuloma closure, a large number of different T cells are recruited to the lesion. At the same time, the TCR repertoire is selected, because AND TCR transgenic T cells (Valpha11/Vbeta3 anti-pigeon cytochrome c) are preferentially excluded from granulomas of BCG-infected AND mice, and cells expressing secondary endemic Vbeta-chains are enriched among AND cells homing to granulomas. Next, we addressed whether TCR heterogeneity is required for effective granuloma formation. We infected 5CC7/recombinase-activating gene 2(-/-) mice with recombinant BCG that express pigeon cytochrome c peptide in a mycobacterial 19-kDa bacterial surface lipoprotein. A CD4(+) T cell with a single specificity in the absence of CD8(+) T cells is sufficient to form granulomas and adequately control bacteria. Our study shows that expanded monoclonal T cell populations can be protective in mycobacterial infection.

译文

肉芽肿的形成是需要CD4()T细胞的迟发型超敏反应的一种形式。肉芽肿控制病原体的生长和传播,防止宿主发炎损害周围组织。我们使用牛分枝杆菌菌株卡介苗(BCG)感染的小鼠模型研究了肝肉芽肿中T细胞异质性的程度。我们证明,即使在单个肉芽肿水平上,肉芽肿浸润性T细胞的TCR谱也非常多样化,这表明在肉芽肿闭合之前,大量不同的T细胞被募集到病变处。同时,选择TCR曲目,是因为从BCG感染的AND小鼠肉芽肿中优先排除了AND TCR转基因T细胞(Valpha11 / Vbeta3抗鸽子细胞色素c),并且表达次级地方性Vbeta链的细胞富集了AND细胞归巢为肉芽肿。接下来,我们探讨了有效形成肉芽肿是否需要TCR异质性。我们用重组BCG感染5CC7 /重组酶激活基因2(-/-)小鼠,该BCG在分枝杆菌19-kDa细菌表面脂蛋白中表达鸽子细胞色素c肽。在没有CD8(T)细胞的情况下,具有单一特异性的CD4(T)细胞足以形成肉芽肿并充分控制细菌。我们的研究表明,扩大的单克隆T细胞群体可以在分枝杆菌感染中起到保护作用。

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