Characterization of a Human Cervical CD4+ T Cell Subset Coexpressing Multiple Markers of HIV Susceptibility
Characterization of a Human Cervical CD4+ T Cell Subset Coexpressing Multiple Markers of HIV Susceptibility
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DOI：
10.4049/jimmunol.1101836
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发表时间：
2011-12-01
影响因子：
4.4
通讯作者：
Kaul, Rupert
中科院分区：
文献类型：
--
作者：
McKinnon, Lyle R.;Nyanga, Billy;Kaul, Rupert
艾滋病毒大流行病对妇女的影响特别大，大多数感染是通过接受性阴道性交获得的。虽然HIV在女性生殖道中建立感染的靶细胞仍然不清楚，但已知免疫激活导致CD 4（+）T细胞具有增强的易感性，粘膜整合素α 4 β 7和HIV辅助受体CCR 5的表达也是如此。从肯尼亚内罗毕的女性性工作者（FSW）中采集血液和宫颈细胞刷标本。进行生殖器感染诊断，基于与粘膜归巢和/或HIV获得相关的表面受体的表达，通过多参数流式细胞术确定T细胞群，并通过细胞内细胞因子染色测定细胞因子产生。26.0%的宫颈CD 4 + T细胞表达整合素α 4 β 7，这些细胞更可能表达HIV辅助受体CCR 5（p < 0.0001）和早期活化标志物CD 69（p <0.0001），但不表达CXCR 4（p = 0.34）。与血液相比，宫颈Th 17频率增强（7.02 vs 1.24%; p < 0.0001），宫颈IL-17 A（+）CD 4（+）T细胞优先共表达α 4 β 7和CCR 5。IFN-γ和IL-22在宫颈Th 17细胞中的表达高于血液Th 17细胞。与这些细胞是优先HIV靶的假设一致，gp 120优先结合CCR 5（+）宫颈T细胞，并且与HIV-FSW相比，HIV+ FSW中宫颈Th 17细胞几乎完全耗尽。综上所述，宫颈粘膜中Th 17 CD 4（+）T细胞亚群共表达多种HIV易感性标志物; HIV感染后它们的急剧耗竭表明这些细胞可能在HIV传播过程中作为关键靶细胞。免疫学杂志，2011，187：6032-6042.
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 alpha 4 beta 7 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 alpha 4 beta 7 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 alpha 4 beta 7 and CCR5. Expression of IFN-gamma 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. The Journal of Immunology, 2011, 187: 6032-6042.