Freeman Michael L, Morris Stephen R, Lederman Michael M
Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, Ohio.
Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio.
Pathog Immun. 2017;2(3):335-351. doi: 10.20411/pai.v2i3.136. Epub 2017 Aug 7.
Mucosa-associated invariant T (MAIT) cells are a recently identified class of innate-like T cells that are involved in the mucosal immune response. MAIT cells are characterized by expression of TCR Vα7.2 and CD161. In HIV infection, there is a profound early loss of MAIT cells from the circulation that never fully recovers, even after prolonged viral control with antiretroviral therapy (ART).
We analyzed PBMCs from fresh whole blood from HIV-negative or ART-treated HIV-positive donors with full (Immune Success) or impaired (Immune Failure) CD4 T- cell recovery by flow cytometry for T-cell markers, TCR Vα7.2, and CD161. The PBMCs were cultured with or without TCR-mediated stimulation, and CD161 expression was assessed on Vα7.2 T cells. Interferon-γ (IFNγ) production was assessed by intracellular cytokine staining.
We found a decrease in the percentage of CD3 T cells that expressed CD161 and the percentage of Vα7.2 T cells that expressed CD161, in HIV-infected individuals. We also found a significant increase in the percentage of T cells that were Vα7.2CD161- in immune failure compared to controls, accompanied by an increase in the percentage of Vα7.2CD161- T cells that express CD8 in donors with immune failure, but not immune success. After TCR stimulation in vitro, Vα7.2 T cells reduced expression of CD161, yet Vα7.2CD161- cells from immune failure donors retained the ability to express IFNγ on stimulation.
Our findings suggest that in immune failure patients, the reduction in peripheral MAIT cells is due, at least in part, to a loss in CD161 expression, and is not merely the result of trafficking into mucosal tissues or cell death. These CD161- cells retain their function.
黏膜相关恒定T（MAIT）细胞是最近发现的一类固有样T细胞，参与黏膜免疫反应。MAIT细胞的特征是表达TCR Vα7.2和CD161。在HIV感染中，循环中的MAIT细胞在早期会大量丧失，即使在通过抗逆转录病毒疗法（ART）长期控制病毒后也从未完全恢复。
我们通过流式细胞术分析了来自HIV阴性或接受ART治疗的HIV阳性供体的新鲜全血中的外周血单核细胞（PBMC），这些供体的CD4 T细胞恢复情况良好（免疫成功）或受损（免疫失败），检测了T细胞标志物、TCR Vα7.2和CD161。PBMC在有或无TCR介导的刺激下进行培养，并评估Vα7.2 T细胞上的CD161表达。通过细胞内细胞因子染色评估干扰素-γ（IFNγ）的产生。
我们发现，在HIV感染个体中，表达CD161的CD3 T细胞百分比以及表达CD161的Vα7.2 T细胞百分比均下降。我们还发现，与对照组相比，免疫失败组中Vα7.2CD161- T细胞的百分比显著增加，同时在免疫失败而非免疫成功的供体中，表达CD8的Vα7.2CD161- T细胞百分比也增加。在体外TCR刺激后，Vα7.2 T细胞的CD161表达降低，但免疫失败供体的Vα7.2CD161-细胞在刺激后仍保留表达IFNγ的能力。
我们的研究结果表明，在免疫失败患者中，外周MAIT细胞的减少至少部分是由于CD161表达的丧失，而不仅仅是迁移到黏膜组织或细胞死亡的结果。这些CD161-细胞保留了它们的功能。
