DataSheet_1_MR1-Restricted MAIT Cells From The Human Lung Mucosal Surface Have Distinct Phenotypic, Functional, and Transcriptomic Features That Are Preserved in HIV Infection.pdf

Mucosal associated invariant T (MAIT) cells are a class of innate-like T cells that utilize a semi-invariant αβ T cell receptor to recognize small molecule ligands produced by bacteria and fungi. Despite growing evidence that immune cells at mucosal surfaces are often phenotypically and functionally distinct from those in the peripheral circulation, knowledge about the characteristics of MAIT cells at the lung mucosal surface, the site of exposure to respiratory pathogens, is limited. HIV infection has been shown to have a profound effect on the number and function of MAIT cells in the peripheral blood, but its effect on lung mucosal MAIT cells is unknown. We examined the phenotypic, functional, and transcriptomic features of major histocompatibility complex (MHC) class I-related (MR1)-restricted MAIT cells from the peripheral blood and bronchoalveolar compartments of otherwise healthy individuals with latent Mycobacterium tuberculosis (Mtb) infection who were either HIV uninfected or HIV infected. Peripheral blood MAIT cells consistently co-expressed typical MAIT cell surface markers CD161 and CD26 in HIV-negative individuals, while paired bronchoalveolar MAIT cells displayed heterogenous expression of these markers. Bronchoalveolar MAIT cells produced lower levels of pro-inflammatory cytokine IFN-γ and expressed higher levels of co-inhibitory markers PD-1 and TIM-3 than peripheral MAIT cells. HIV infection resulted in decreased frequencies and pro-inflammatory function of peripheral blood MAIT cells, while in the bronchoalveolar compartment MAIT cell frequency was decreased but phenotype and function were not significantly altered. Single-cell transcriptomic analysis demonstrated greater heterogeneity among bronchoalveolar compared to peripheral blood MAIT cells and suggested a distinct subset in the bronchoalveolar compartment. The transcriptional features of this bronchoalveolar subset were associated with MAIT cell tissue repair functions. In summary, we found previously undescribed phenotypic and transcriptional heterogeneity of bronchoalveolar MAIT cells in HIV-negative people. In HIV infection, we found numeric depletion of MAIT cells in both anatomical compartments but preservation of the novel phenotypic and transcriptional features of bronchoalveolar MAIT cells.

黏膜相关不变性T（MAIT）细胞是一类类似于先天免疫的T细胞，它们通过半不变性的αβT细胞受体识别由细菌和真菌产生的低分子量配体。尽管越来越多的证据表明，黏膜表面的免疫细胞在表型和功能上通常与外周循环中的免疫细胞有所不同，但对于暴露于呼吸道病原体的肺部黏膜表面MAIT细胞特性的了解仍然有限。HIV感染已被证实对周围血液中MAIT细胞的数量和功能有深远的影响，但其对肺部黏膜MAIT细胞的影响尚不清楚。本研究调查了潜伏性结核分枝杆菌（Mtb）感染且未感染HIV或感染HIV的健康个体的外周血和支气管肺泡间隙中，MHC I类相关（MR1）限制性MAIT细胞的表型、功能和转录组特征。在外周血中，MAIT细胞在HIV阴性个体中持续共表达典型的MAIT细胞表面标记CD161和CD26，而配对的支气管肺泡MAIT细胞则表现出这些标记的异质性表达。与外周MAIT细胞相比，支气管肺泡MAIT细胞产生的促炎细胞因子IFN-γ水平较低，而共抑制性标记PD-1和TIM-3的表达水平较高。HIV感染导致外周血MAIT细胞的频率和促炎功能降低，而在支气管肺泡间隙中，MAIT细胞的频率降低，但其表型和功能没有显著改变。单细胞转录组分析显示，与外周血MAIT细胞相比，支气管肺泡MAIT细胞具有更高的异质性，并暗示支气管肺泡间隙中存在一个独特的亚群。该亚群的转录特征与MAIT细胞的组织修复功能相关。总之，本研究在HIV阴性人群中发现了支气管肺泡MAIT细胞先前未描述的表型和转录组异质性。在HIV感染中，我们发现在两个解剖部位中MAIT细胞数量均减少，但支气管肺泡MAIT细胞的 novel 表型和转录组特征得以保留。