Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection
Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection
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DOI：
10.1182/blood-2012-07-445429
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发表时间：
2013-02-14
期刊：
影响因子：
20.3
通讯作者：
Sandberg, Johan K.
中科院分区：
文献类型：
--
作者：
Leeansyah, Edwin;Ganesh, Anupama;Sandberg, Johan K.
粘膜相关不变T（MAIT）细胞是进化上保守的抗微生物MR 1限制性T细胞亚群。MAIT细胞是CD 161（+），表达V α 7.2 TCR，主要是CD 8（+），并且在血液和粘膜组织中大量存在。然而，它们在HIV-1感染中的作用尚不清楚。在这项研究中，我们发现MAIT细胞水平在慢性HIV-1感染患者的循环中严重减少。残留的MAIT细胞高度活化，功能耗尽。它们的下降与自诊断以来的时间、活化水平以及伴随的功能受损的CD 161（-）V α 7.2（+）T细胞亚群的扩增有关。通过将MAIT细胞暴露于大肠杆菌在体外产生这样的细胞。值得注意的是，虽然残留的MAIT细胞的功能至少部分恢复了有效的抗逆转录病毒治疗，MAIT细胞在外周血中的水平没有恢复。有趣的是，直肠粘膜中的MAIT细胞相对保存，尽管在血液中观察到的一些变化在粘膜中重现。这些发现与MAIT细胞隔室的模型一致，可能是由于持续暴露于微生物材料，在慢性HIV-1感染期间被参与、激活、耗尽并逐渐持续耗尽。（血。2013; 121（7）：1124-1135）
Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved antimicrobial MR1-restricted T-cell subset. MAIT cells are CD161(+), express a V alpha 7.2 TCR, are primarily CD8(+) and numerous in blood and mucosal tissues. However, their role in HIV-1 infection is unknown. In this study, we found levels of MAIT cells to be severely reduced in circulation in patients with chronic HIV-1 infection. Residual MAIT cells were highly activated and functionally exhausted. Their decline was associated with time since diagnosis, activation levels, and the concomitant expansion of a subset of functionally impaired CD161(-) V alpha 7.2(+) T cells. Such cells were generated in vitro by exposure of MAIT cells to Escherichia coli. Notably, whereas the function of residual MAIT cells was at least partly restored by effective antiretroviral therapy, levels of MAIT cells in peripheral blood were not restored. Interestingly, MAIT cells in rectal mucosa were relatively preserved, although some of the changes seen in blood were recapitulated in the mucosa. These findings are consistent with a model in which the MAIT-cell compartment, possibly as a result of persistent exposure to microbial material, is engaged, activated, exhausted, and progressively and persistently depleted during chronic HIV-1 infection. (Blood. 2013; 121(7): 1124-1135)