Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Victoria 3000, Australia;
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Victoria 3000, Australia.
J Immunol. 2019 Apr 1;202(7):2105-2120. doi: 10.4049/jimmunol.1801405. Epub 2019 Feb 18.
Mucosal-associated invariant T (MAIT) cells are nonconventional T lymphocytes that recognize bacterial metabolites presented by MR1. Whereas gut bacterial translocation and the loss/dysfunction of peripheral MAIT cells in HIV infection is well described, MAIT cells in nonhuman primate models are poorly characterized. We generated a pigtail macaque (PTM)-specific MR1 tetramer and characterized MAIT cells in serial samples from naive and SIV- or simian HIV-infected PTM. Although PTM MAIT cells generally resemble the phenotype and transcriptional profile of human MAIT cells, they exhibited uniquely low expression of the gut-homing marker α4β7 and were not enriched at the gut mucosa. PTM MAIT cells responded to SIV/simian HIV infection by proliferating and upregulating α4β7, coinciding with increased MAIT cell frequency in the rectum. By 36 wk of infection, PTM MAIT cells were activated and exhibited a loss of Tbet expression but were not depleted as in HIV infection. Our data suggest the following: 1) MAIT cell activation and exhaustion is uncoupled from the hallmark depletion of MAIT cells during HIV infection; and 2) the lack of PTM MAIT cell enrichment at the gut mucosa may prevent depletion during chronic infection, providing a model to assess potential immunotherapeutic approaches to modify MAIT cell trafficking during HIV infection.
黏膜相关不变 T（MAIT）细胞是非传统的 T 淋巴细胞，可识别由 MR1 呈递的细菌代谢产物。虽然肠道细菌易位和 HIV 感染中外周 MAIT 细胞的丧失/功能障碍已有很好的描述，但非人类灵长类动物模型中的 MAIT 细胞特征描述较少。我们生成了一种针对恒河猴（PTM）的特异性 MR1 四聚体，并对来自未感染和 SIV 或猴免疫缺陷病毒（simian HIV）感染的 PTM 的连续样本中的 MAIT 细胞进行了特征描述。尽管 PTM MAIT 细胞通常与人类 MAIT 细胞的表型和转录谱相似，但它们表现出独特的低水平表达肠道归巢标志物α4β7，并且不在肠道黏膜处富集。PTM MAIT 细胞通过增殖和上调α4β7 对 SIV/simian HIV 感染作出反应，同时直肠中 MAIT 细胞频率增加。在感染 36 周时，PTM MAIT 细胞被激活并表现出 Tbet 表达的丧失，但不会像在 HIV 感染中那样被耗尽。我们的数据表明：1）MAIT 细胞的激活和耗竭与 HIV 感染期间 MAIT 细胞耗竭的标志性特征脱钩；2）缺乏 PTM MAIT 细胞在肠道黏膜处的富集可能会防止在慢性感染期间被耗尽，为评估在 HIV 感染期间改变 MAIT 细胞迁移的潜在免疫治疗方法提供了模型。
