Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa
Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa
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DOI：
10.1038/s41467-019-12732-2
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发表时间：
2019-10-18
影响因子：
16.6
通讯作者：
Genesca, Meritxell
中科院分区：
文献类型：
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作者：
Cantero-Perez, Jon;Grau-Exposito, Judith;Genesca, Meritxell
HIV病毒库在感染过程的早期就已建立。常驻记忆 T 细胞 (T-RM) 存在于女性下生殖道等组织中，但该细胞亚群对 HIV 发病机制和持续存在的贡献仍不清楚。在这里，我们发现宫颈CD4(+)T(RM)显示出独特的分化簇，其中富集了与HIV感染易感性、寿命和自我更新能力相关的几种分子。这些蛋白质谱富含表达 CD32 的 CD4(+)T(RM) 的一部分。宫颈外植体模型显示，CD4(+)T(RM) 优先支持 HIV 感染，并且比非 T-RM 含有更多的病毒 DNA 和蛋白质。重要的是，接受 ART 抑制的 HIV+ 女性的宫颈组织含有高水平的病毒 DNA 和 RNA，这是 TRM 部分的主要贡献者。这些结果认识到女性下生殖道是艾滋病毒的避难所，并将 CD4(+)T(RM) 确定为艾滋病毒感染和病毒持续存在的主要目标。因此，HIV 治愈策略需要考虑广泛分布于组织中的 T-RM 表型。
HIV viral reservoirs are established very early during infection. Resident memory T cells (T-RM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4(+)T(RM) display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities. These protein profiles are enriched in a fraction of CD4(+)T(RM) expressing CD32. Cervical explant models show that CD4(+)T(RM) preferentially support HIV infection and harbor more viral DNA and protein than non-T-RM. Importantly, cervical tissue from ART-suppressed HIV+ women contain high levels of viral DNA and RNA, being the TRM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4(+)T(RM) as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider T-RM phenotypes, which are widely distributed in tissues.