Differential localization and limited cytotoxic potential of duodenal CD8+ T cells.
Differential localization and limited cytotoxic potential of duodenal CD8+ T cells.
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DOI：
10.1172/jci.insight.154195
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发表时间：
2022-02-08
期刊：
影响因子：
8
通讯作者：
Ndhlovu ZM
中科院分区：
文献类型：
--
作者：
Mvaya L;Khaba T;Lakudzala AE;Nkosi T;Jambo N;Kadwala I;Kankwatira A;Patel PD;Gordon MA;Nyirenda TS;Jambo KC;Ndhlovu ZM
十二指肠是抑制性抗逆转录病毒治疗期间HIV持续存在的主要部位，尽管其具有丰富的组织驻留记忆（Trm）CD 8 + T细胞。十二指肠Trm CD 8 + T细胞在病毒控制中的作用仍然没有很好的定义。我们研究了HIV感染者（PLHIV）和健康对照者的人十二指肠组织中CD 8 + T细胞的空间定位、表型和功能。我们发现Trm（CD 69 + CD 103 hi）细胞是十二指肠中主要的CD 8 + T细胞群。免疫荧光成像显示，CD 103 + CD 8 + T细胞定位于上皮内区域，而CD 103-CD 8 + T细胞和CD 4 + T细胞主要定位于固有层（LP）。此外，HIV特异性CD 8 + T细胞在CD 69 + CD 103-/lo群体中富集。然而，十二指肠HIV特异性CD 8 + Trm细胞很少表达具有强效细胞溶解功能的典型分子（穿孔素和颗粒酶B），但比外周血中的细胞功能更强。总之，我们的研究结果表明，十二指肠CD 8 + Trm细胞具有有限的穿孔素介导的细胞溶解潜力，并在空间上与HIV易感LP CD 4 + T细胞分离。这可能有助于艾滋病毒在十二指肠的持久性，并为治愈疗法的设计提供了关键信息。
The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8+ T cells. The role of duodenal Trm CD8+ T cells in viral control is still not well defined. We examined the spatial localization, phenotype, and function of CD8+ T cells in the human duodenal tissue from people living with HIV (PLHIV) and healthy controls. We found that Trm (CD69+CD103hi) cells were the predominant CD8+ T cell population in the duodenum. Immunofluorescence imaging of the duodenal tissue revealed that CD103+CD8+ T cells were localized in the intraepithelial region, while CD103–CD8+ T cells and CD4+ T cells were mostly localized in the lamina propria (LP). Furthermore, HIV-specific CD8+ T cells were enriched in the CD69+CD103–/lo population. However, the duodenal HIV-specific CD8+ Trm cells rarely expressed canonical molecules for potent cytolytic function (perforin and granzyme B) but were more polyfunctional than those from peripheral blood. Taken together, our results show that duodenal CD8+ Trm cells possess limited perforin-mediated cytolytic potential and are spatially separated from HIV-susceptible LP CD4+ T cells. This could contribute to HIV persistence in the duodenum and provides critical information for the design of cure therapies.