CELLULAR IMMUNITY AND PATHOGENESIS OF CHLAMYDIA TRACHOMATIS--PID

由沙眼衣原体引起的盆腔炎是一种重要的 导致妇女生殖健康状况不佳。其发病机制 疾病尚不清楚，需要这方面的新知识来改善 预防和治疗的方法。这个项目的总体目标是 为阐明C. 沙眼衣原体流行病学数据收集自一组 肯尼亚内罗毕的商业性工作者中C. 宫颈沙眼感染和盆腔炎提示 对衣原体感染的细胞免疫反应是 决定了感染的进程据观察，在艾滋病毒 感染的妇女，CD 4细胞的损失显着增加的风险C。 沙眼衣原体同样，一个特定的HLA I类等位基因也独立地被 与C的风险增加有关。沙眼衣原体暗示 CD 8 T淋巴细胞介导组织炎症的作用。基于 这些意见，目前赠款建议继续评估 这群商业性工作者是因为C事件沙眼衣原体 感染和PID病例-将招募300至600名妇女， 估计有50到75名妇女患有C.沙眼PID和200名妇女与 单纯性宫颈衣原体感染将进行细胞 免疫反应。该研究假设CD 4 T细胞可以保护 针对C.沙眼衣原体PID和抗原特异性CD 8 T细胞介导 上生殖道的炎症损伤蜂窝 生殖道的免疫反应-患有PID的女性将 其特征在于收集子宫内膜活检组织并确定 子宫内膜浸润淋巴细胞的免疫表型， 将其与细胞因子/酶特异性mRNA特征相关联， T细胞亚群，CD 4、TH 1、TH 2和CD 8 CTL。宫颈刮片样本 含有渗出性淋巴细胞的细胞也将具有细胞因子/酶 C.妇女T细胞亚群的特异性mRNA。沙眼衣原体 单独宫颈感染的妇女，并与C.沙眼衣原体 对于子宫内膜和宫颈样本，将使用RT-PCR来 表征细胞因子/酶mRNA模式。总的来说，数据将 阐明了CD 8细胞毒性T淋巴细胞在发病机制中的作用 梭沙眼衣原体PID和潜在的机制，CD 4 T 淋巴细胞提供针对C.沙眼衣原体

Pelvic inflammatory disease due to Chlamydia trachomatis is an important cause of poor reproductive health for women. The pathogenesis for this disease is unclear and new knowledge in this area is needed to improve approaches for prevention and treatment. The overall goal of this proposal is to elucidate the cellular immune pathogenesis of C. trachomatis PID. Epidemiological data collected from a group of commercial sex workers in Nairobi, Kenya who have a high incidence of C. trachomatis cervical infection and pelvic inflammatory disease suggest that cellular immune responses to chlamydia infection are pivotal in determining the course of this infection. It was observed that among HIV infected women, CD4 cell loss dramatically increased the risk of C. trachomatis PID. As well, a specific HLA class I allele was independently associated with an increased risk of C. trachomatis PID. suggesting a role for CD8 T lymphocytes in mediating tissue inflammation. Based on these observations, the present grant proposes to continue to evaluate this cohort of commercial sex workers for incident C. trachomatis infection and PID cases- Between 300 and 600 women will be enrolled and an estimated 50 to 75 women with C. trachomatis PID and 200 women with uncomplicated cervical chlamydia infection will be evaluated for cellular immune responses. The study hypothesis is that CD4 T cells protect against C. trachomatis PID and that antigen specific CD8 T cells mediate the inflammatory damage to the upper reproductive tract. The cellular immune response in the reproductive tract among-women with PID will be characterized by collecting endometrial biopsy tissue and determining the immunophenotypes of lymphocytes infiltrating the endometrium and correlating this with cytokine/enzyme specific mRNA characteristic of the T cell subsets, CD4 TH1, TH2 and CD8 CTLs. Cervical scrape samples containing exudative lymphocytes will also have the cytokine/enzyme specific mRNA for T cell subsets determined for women with C. trachomatis cervical infection alone and compared to women with C. trachomatis PID. For both endometrial and cervical samples, RT-PCR will be used to characterize cytokine/enzyme mRNA patterns. In aggregate, the data will shed light on the role of CD8 cytotoxic T lymphocytes in the pathogenesis of C. trachomatis PID and the potential mechanisms by which CD4 T lymphocytes confer protection against C. trachomatis PID.