Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5A 1A8.
J Immunol. 2011 Dec 1;187(11):6032-42. doi: 10.4049/jimmunol.1101836. Epub 2011 Nov 2.
The HIV pandemic disproportionately affects women, with most infections acquired through receptive vaginal sex. Although the target cells by which HIV establishes infection in the female genital tract remain poorly defined, it is known that immune activation results in CD4(+) T cells with enhanced susceptibility, as does expression of the mucosal integrin α4β7 and the HIV coreceptor CCR5. Blood and cervical cytobrush specimens were collected from female sex workers (FSWs) in Nairobi, Kenya. Genital infection diagnostics were performed, T cell populations were defined by multiparameter flow cytometry based on their expression of surface receptors relevant to mucosal homing and/or HIV acquisition, and cytokine production was assayed by intracellular cytokine staining. The integrin α4β7 was expressed on 26.0% of cervical CD4(+) T cells, and these cells were more likely to express both the HIV coreceptor CCR5 (p < 0.0001) and the early activation marker CD69 (p < 0.0001) but not CXCR4 (p = 0.34). Cervical Th17 frequencies were enhanced compared with blood (7.02 versus 1.24%; p < 0.0001), and cervical IL-17A(+) CD4(+) T cells preferentially coexpressed α4β7 and CCR5. Expression of IFN-γ and IL-22 was greater in cervical Th17 cells than in blood Th17 cells. In keeping with the hypothesis that these cells are preferential HIV targets, gp120 preferentially bound CCR5(+) cervical T cells, and cervical Th17 cells were almost completely depleted in HIV(+) FSWs compared with HIV(-) FSWs. In summary, a subset of Th17 CD4(+) T cells in the cervical mucosa coexpresses multiple HIV susceptibility markers; their dramatic depletion after HIV infection suggests that these may serve as key target cells during HIV transmission.
艾滋病毒疫情对女性的影响不成比例，大多数感染是通过接受阴道性交获得的。尽管女性生殖道中 HIV 感染的靶细胞仍未得到明确界定，但已知免疫激活导致 CD4(+)T 细胞易感性增强，黏膜整合素 α4β7 和 HIV 共受体 CCR5 的表达也是如此。从肯尼亚内罗毕的性工作者 (FSW) 中采集了血液和宫颈细胞刷标本。进行了生殖道感染诊断，通过多参数流式细胞术根据与黏膜归巢和/或 HIV 获得相关的表面受体表达定义 T 细胞群体，并通过细胞内细胞因子染色测定细胞因子产生。整合素 α4β7 表达于 26.0%的宫颈 CD4(+)T 细胞上，这些细胞更有可能同时表达 HIV 共受体 CCR5(p < 0.0001)和早期激活标志物 CD69(p < 0.0001)，但不表达 CXCR4(p = 0.34)。与血液相比，宫颈 Th17 频率升高 (7.02 比 1.24%;p < 0.0001)，且宫颈 IL-17A(+)CD4(+)T 细胞优先共表达 α4β7 和 CCR5。宫颈 Th17 细胞中 IFN-γ 和 IL-22 的表达高于血液 Th17 细胞。与这些细胞是 HIV 优先靶细胞的假设一致，gp120 优先结合 CCR5(+)宫颈 T 细胞，与 HIV(-)FSW 相比，HIV(+)FSW 中宫颈 Th17 细胞几乎完全耗尽。总之，宫颈黏膜中的一部分 Th17 CD4(+)T 细胞共同表达多种 HIV 易感性标志物；它们在 HIV 感染后大量耗竭表明，这些细胞在 HIV 传播过程中可能作为关键靶细胞。
