Fernandez Caroline S, Amarasena Thakshila, Kelleher Anthony D, Rossjohn Jamie, McCluskey James, Godfrey Dale I, Kent Stephen J
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
1] Kirby Institute, University of New South Wales, Darlinghurst, New South Wales, Australia [2] St Vincent's Centre for Applied Medical Research, Sydney, New South Wales, Australia.
Immunol Cell Biol. 2015 Feb;93(2):177-88. doi: 10.1038/icb.2014.91. Epub 2014 Oct 28.
Mucosal-associated invariant T (MAIT) cells home to mucosal sites and exert antimicrobial activity against bacteria and other microorganisms. HIV infection leads to early depletion of gut T cells and translocation of bacterial products. There are reports that MAIT cells, defined by coexpression of Vα7.2 and CD161, are depleted during HIV infection and residual MAIT cells are functionally impaired. However, one study suggested that MAIT cells might remain after HIV infection but evade detection through CD161 downregulation. Thus, the impact of HIV infection on MAIT cells is unclear. We studied longitudinal blood samples from 31 HIV-infected subjects for MAIT cell numbers, phenotype and function using both standard Vα7.2/CD161 surface markers and an MR1 tetramer. We found that MAIT cells were depleted early during HIV infection, and although there was a concomitant rise in Vα7.2(+)CD161(-) cells, these were MR1 tetramer negative, indicating that these are unlikely to be altered MAIT cells. Antigen-mediated activation of residual MAIT cells showed that they remained functional out to 2 years following HIV infection. Although MAIT cells are depleted in HIV infection, residual and functionally active MAIT cells persist and may still be able to assist in controlling bacterial translocation during HIV infection.
黏膜相关恒定T(MAIT)细胞归巢至黏膜部位,并对细菌和其他微生物发挥抗菌活性。HIV感染导致肠道T细胞早期耗竭以及细菌产物的易位。有报道称,由Vα7.2和CD161共表达所定义的MAIT细胞在HIV感染期间会减少,且残留的MAIT细胞功能受损。然而,一项研究表明,MAIT细胞在HIV感染后可能仍然存在,但通过CD161下调逃避检测。因此,HIV感染对MAIT细胞的影响尚不清楚。我们使用标准的Vα7.2/CD161表面标志物和MR1四聚体,研究了31名HIV感染受试者的纵向血液样本中的MAIT细胞数量、表型和功能。我们发现,MAIT细胞在HIV感染早期就会减少,尽管Vα7.2(+)CD161(-)细胞同时增加,但这些细胞MR1四聚体阴性,表明这些不太可能是改变后的MAIT细胞。抗原介导的残留MAIT细胞激活表明,在HIV感染后2年内它们仍保持功能。尽管MAIT细胞在HIV感染中会减少,但残留且功能活跃的MAIT细胞持续存在,并且在HIV感染期间可能仍能够协助控制细菌易位。