Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Immunology. 2009 Sep;128(1 Suppl):e746-57. doi: 10.1111/j.1365-2567.2009.03077.x. Epub 2009 Mar 26.
Cervical cytobrush sampling is a relatively non-invasive method for obtaining mucosal cells from the female genital tract. To define mucosal immune cells sampled by cervical cytobrushing and to validate this approach for local immunity studies, we investigated the impact of human immunodeficiency virus (HIV) status and inflammation on the yield and composition of cervical cytobrush specimens. Cervical cytobrush samples were obtained from 89 chronically HIV-infected and 46 HIV-negative women. The HIV-infected women had significantly higher yields of CD3(+), CD45(+), CD19(+), CD14(+), Langerin(+) and CD24(+) cells than the uninfected women. While cytobrush-derived T cells from uninfected women were predominantly CD4(+) (4.2 CD4 : 1 CD8), CD8(+) T cells were predominant in HIV-infected women (0.6 CD4 : 1 CD8). The majority of CD4(+) and CD8(+) T cells from HIV-infected and uninfected women were of the effector memory (CD45RA(-) CCR7(-) CD27(-)) phenotype. HIV-infected women had significantly elevated levels of interleukin (IL)-1beta, IL-6 and IL-8 in cervical supernatants compared with uninfected women. We observed a significant positive correlation between T-cell counts and IL-1beta, tumour necrosis factor (TNF)-alpha and IL-12 concentrations. Neutrophil counts correlated significantly with cervical concentrations of IL-1beta, TNF-alpha, IL-8, IL-6 and IL-10. Antigen-presenting cell numbers correlated significantly with TNF-alpha and IL-12 concentrations. HIV-infected women on antiretroviral therapy had similar levels of cervical lymphocyte infiltration and inflammation to women naïve to therapy. In conclusion, we suggest that inflammation at the cervix and HIV infection are likely to be key determinants in the absolute number of mucosal immune cells recovered by cervical cytobrushing.
宫颈刷采样是一种相对无创的方法,可从女性生殖道获得黏膜细胞。为了定义宫颈刷取样的黏膜免疫细胞,并验证这种方法用于局部免疫研究,我们研究了人类免疫缺陷病毒(HIV)状态和炎症对宫颈刷标本产量和组成的影响。从 89 名慢性 HIV 感染和 46 名 HIV 阴性的女性中获得了宫颈刷样本。与未感染的女性相比,HIV 感染的女性的 CD3(+)、CD45(+)、CD19(+)、CD14(+)、朗格汉斯细胞(Langerin(+))和 CD24(+)细胞的产量明显更高。虽然未感染女性的宫颈刷衍生 T 细胞主要是 CD4(+)(4.2 CD4:1 CD8),但 HIV 感染的女性中 CD8(+) T 细胞占优势(0.6 CD4:1 CD8)。HIV 感染和未感染的女性的大多数 CD4(+)和 CD8(+)T 细胞均为效应记忆表型(CD45RA(-) CCR7(-) CD27(-))。与未感染的女性相比,HIV 感染的女性的宫颈上清液中白细胞介素(IL)-1beta、IL-6 和 IL-8 的水平显著升高。我们观察到 T 细胞计数与 IL-1beta、肿瘤坏死因子(TNF)-alpha 和 IL-12 浓度之间存在显著的正相关。中性粒细胞计数与宫颈中 IL-1beta、TNF-alpha、IL-8、IL-6 和 IL-10 的浓度显著相关。抗原呈递细胞数量与 TNF-alpha 和 IL-12 浓度显著相关。接受抗逆转录病毒治疗的 HIV 感染女性与未经治疗的女性相比,宫颈淋巴细胞浸润和炎症程度相似。总之,我们认为宫颈炎症和 HIV 感染可能是宫颈刷取样中黏膜免疫细胞绝对数量的关键决定因素。