Yeaman G R, White H D, Howell A, Prabhala R, Wira C R
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA.
AIDS Res Hum Retroviruses. 1998 Apr;14 Suppl 1:S57-62.
Using isolated cell suspensions and in situ techniques, we have partially characterized the organization, functional capacity, and sex hormone regulation of the mucosal immune system in the human female reproductive tract. Isolated cells suspensions have been used to demonstrate that the uterus contains antigen-presenting cells that are functionally able to present antigen to autologous tetanus toxoid-specific T cells. Immunophenotypic analyses of the female reproductive tract by three-color immunofluorescent staining has been used to show that lymphoid aggregates, which are absent in postmenopausal women, develop in the uterine endometrium during the menstrual cycle in premenopausal women. Lymphoid aggregates are composed of a B lymphocyte core surrounded by numerous CD8+CD4- T lymphocytes and an outer halo of macrophages. Macrophages, CD4+ and CD8+ T cells, and CD56+ NK cells are distributed throughout the uterine endometrium. In contrast, the Fallopian tube, cervix, and vagina, which lack lymphoid aggregates, contain CD8+ and CD4+ T cells as well as macrophages. The female reproductive tract has also been analyzed for the presence of antigen-independent CD3+ T lymphocyte cytolytic function by an anti-CD3 MAb-mediated redirected lysis assay. High levels of CD3+ T lymphocyte cytolytic activity were demonstrated in cervix and vagina and independent of stage of the menstrual cycle. In the uterus, cytolytic activity changed with endocrine state. In postmenopausal women the uterine endometrium had CD3+ T lymphocytes with high cytolytic activity, whereas premenopausal women had CD3+ T lymphocytes with moderate cytolytic potential during the proliferative phase to low/no cytolytic activity during the secretory phase of the menstrual cycle. In studies to determine whether the upper reproductive tract could be infected with HIV-1, we found on the basis of nef expression and p24 release that epithelial cells from the Fallopian tube, and from the uterus and cervix, are infectable. These studies demonstrate that the human female reproductive tract is an inductive site for immune responses and the cell-mediated immunity is present throughout the female reproductive tract. These studies further indicate that the Fallopian tube and uterus are potential entry sites for HIV-1 infection and that uterine immune cell architecture as well as cytolytic activity are under hormonal control.
利用分离的细胞悬液和原位技术，我们已部分阐明了人类女性生殖道黏膜免疫系统的组织结构、功能能力及性激素调节。分离的细胞悬液已用于证明子宫含有抗原呈递细胞，这些细胞在功能上能够将抗原呈递给自体破伤风类毒素特异性T细胞。通过三色免疫荧光染色对女性生殖道进行免疫表型分析，结果显示绝经后女性子宫内膜中不存在的淋巴样聚集物，在绝经前女性的月经周期中会在子宫内膜中形成。淋巴样聚集物由一个B淋巴细胞核心组成，周围是大量CD8 + CD4 - T淋巴细胞和一圈外周巨噬细胞。巨噬细胞、CD4 + 和CD8 + T细胞以及CD56 + NK细胞分布于整个子宫内膜。相比之下，缺乏淋巴样聚集物的输卵管、子宫颈和阴道含有CD8 + 和CD4 + T细胞以及巨噬细胞。通过抗CD3单克隆抗体介导的重定向裂解试验，还分析了女性生殖道中是否存在抗原非依赖性CD3 + T淋巴细胞的细胞溶解功能。在子宫颈和阴道中证实存在高水平的CD3 + T淋巴细胞细胞溶解活性，且与月经周期阶段无关。在子宫中，细胞溶解活性随内分泌状态而变化。绝经后女性的子宫内膜中CD3 + T淋巴细胞具有高细胞溶解活性，而绝经前女性在月经周期的增殖期CD3 + T淋巴细胞具有中等细胞溶解潜能，在分泌期则具有低/无细胞溶解活性。在确定上生殖道是否可被HIV - 1感染的研究中，我们基于nef表达和p24释放发现，输卵管、子宫和子宫颈的上皮细胞是可感染的。这些研究表明，人类女性生殖道是免疫反应的诱导部位，且细胞介导的免疫存在于整个女性生殖道。这些研究进一步表明，输卵管和子宫是HIV - 1感染的潜在进入部位，且子宫免疫细胞结构以及细胞溶解活性受激素控制。
