Abstract:
Previous studies have indicated that the loss of CD161-expressing CD4+ Th17 cells is linked to the progression of chronic HIV. These cells are significantly depleted in peripheral blood and gut mucosa of HIV-infected individuals, contributing to inflammation and disruption of the gut barrier. However, the impact of HIV infection on CD161-expressing CD8+ T cells remain unclear. Here, we examined the functions of peripheral blood and mucosal CD161+CD8+ T cells in the macaque model of HIV infection. In contrast to the significant loss of CD161+CD4+ T cells, CD161+CD8+ T cell frequencies were maintained in blood and gut during chronic SIV infection. Furthermore, gut CD161+CD8+ T cells displayed greater IL-17 production and maintained Th1-type and cytolytic functions, contrary to impaired IL-17 and granzyme-B production in CD161+CD4+ T cells of SIV-infected macaques. These results suggest that augmented Th17-type effector functions of CD161+CD8+ T cells during SIV infection is a likely mechanism to compensate for the sustained loss of gut mucosal Th17 cells. Targeting the cytokine and cytolytic effector functions of CD161+CD8+ T cells in the preclinical setting of chronic SIV infection with antiretroviral therapy has implications in the restoration of gut barrier disruption in persons with HIV infection.
摘要:
先前的研究表明,表达CD161的CD4+Th17细胞的缺失与慢性HIV的进展有关。这些细胞在HIV感染个体的外周血和肠粘膜中显著耗尽,有助于炎症和肠道屏障的破坏。然而,HIV感染对表达CD161的CD8+T细胞的影响尚不清楚.这里,我们检测了HIV感染猕猴模型中外周血和粘膜CD161+CD8+T细胞的功能。与CD161+CD4+T细胞的显著损失相反,CD161+CD8+T细胞频率在慢性SIV感染期间维持在血液和肠道中。此外,肠CD161+CD8+T细胞显示更多的IL-17产生和维持Th1型和细胞溶解功能,与SIV感染的猕猴的CD161CD4T细胞中IL-17和颗粒酶B的产生受损相反。这些结果表明,SIV感染期间CD161CD8T细胞的Th17型效应子功能增强可能是补偿肠粘膜Th17细胞持续损失的机制。在抗逆转录病毒疗法的慢性SIV感染的临床前环境中,靶向CD161CD8T细胞的细胞因子和溶细胞效应功能对HIV感染者肠道屏障破坏的恢复具有意义。