Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden;
J Immunol. 2014 Apr 15;192(8):3947-57. doi: 10.4049/jimmunol.1302826. Epub 2014 Mar 17.
The female genital tract is a portal of entry for sexual HIV transmission and a possible viral reservoir. In this study, the ectocervical CD8+ T cell distribution was explored in situ and was related to expression of CD3 and HLA-DR and presence of HIV RNA. For this purpose, ectocervical tissue samples and genital secretions were collected from HIV-seropositive (HIV+) Kenyan female sex workers (FSWs) (n = 20), HIV-seronegative (HIV-) FSWs (n = 17), and HIV(-) lower-risk women (n = 21). Cell markers were assessed by in situ staining and by quantitative PCR. HIV RNA expression in tissue was analyzed by in situ hybridization, and viral shedding was assessed by quantitative PCR. The HIV+ FSW group had a higher amount of total cells and CD8+, CD3+, and HLA-DR+ cells compared with the HIV(-)FSW group and HIV- lower-risk women. The majority of CD8+ cells were CD3+ T cells, and the numbers of CD8+ cells correlated significantly with plasma and cervical viral load. HIV RNA expression in situ was found in 4 of the 20 HIV+FSW women but did not correlate with cervical or plasma viral load. Thus, the HIV+ women displayed high numbers of CD8+, CD3+, and HLA-DR+ cells, as well as a limited number of HIV RNA+ cells, in their ectocervical mucosa; hence, this localization cannot be neglected as a potential viral reservoir. The elevated levels of CD8+ T cells may play a role in the immunopathogenesis of HIV in the female genital tract.
女性生殖道是性传播 HIV 的入口，也是可能的病毒储存库。在这项研究中，我们原位研究了宫颈外口的 CD8+T 细胞分布，并将其与 CD3 和 HLA-DR 的表达以及 HIV RNA 的存在相关联。为此，我们从 HIV 阳性（HIV+）肯尼亚女性性工作者（FSW）（n=20）、HIV 阴性（HIV-）FSW（n=17）和 HIV-低风险女性（n=21）中收集了宫颈外口组织样本和生殖道分泌物。通过原位染色和定量 PCR 评估细胞标志物。通过原位杂交分析组织中的 HIV RNA 表达，并通过定量 PCR 评估病毒脱落。与 HIV- FSW 组和 HIV-低风险女性相比，HIV+ FSW 组的总细胞数和 CD8+、CD3+和 HLA-DR+细胞数更高。大多数 CD8+细胞是 CD3+T 细胞，CD8+细胞数量与血浆和宫颈病毒载量显著相关。在 20 名 HIV+ FSW 女性中，有 4 名发现了 HIV RNA 的原位表达，但与宫颈或血浆病毒载量无关。因此，HIV+女性在外生殖道黏膜中显示出大量的 CD8+、CD3+和 HLA-DR+细胞，以及数量有限的 HIV RNA+细胞；因此，这个部位不能被忽视为潜在的病毒储存库。高水平的 CD8+T 细胞可能在女性生殖道中 HIV 的免疫发病机制中发挥作用。
