CELLULAR IMMUNITY AND PATHOGENESIS OF CHLAMYDIA TRACHOMATIS--PID

沙眼衣原体的细胞免疫与发病机制

• 批准号: 5205452
• 负责人: ROBERT C BRUNHAM
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5205452
• 关键词: Chlamydia trachomatis; T lymphocyte; antibacterial antibody; biopsy; cellular immunity; cervix; cooperative study; cytokine; cytotoxic T lymphocyte; endometrium; genital secretion; helper T lymphocyte; immunoglobulin A; immunoglobulin G; immunoglobulin M; messenger RNA; pathologic process; pelvic inflammatory disease; polymerase chain reaction; tumor necrosis factor alpha

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.

沙眼衣原体引起的盆腔炎是一种重要的疾病 导致妇女生殖健康状况不佳的原因。此病的发病机制 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。本次活动的总体目标 该提案旨在阐明 C. 的细胞免疫发病机制。 沙眼衣原体 PID。流行病学数据收集自一组 肯尼亚内罗毕的商业性工作者感染念珠菌的几率很高。 沙眼宫颈感染和盆腔炎提示 对衣原体感染的细胞免疫反应至关重要 确定这种感染的过程。据观察，艾滋病毒中 受感染的女性，CD4 细胞损失显着增加了 C. 沙眼衣原体 PID。同样，特定的 HLA I 类等位基因是独立的 与沙眼衣原体 PID 风险增加相关。建议一个 CD8 T 淋巴细胞在介导组织炎症中的作用。基于 根据这些意见，本次赠款建议继续评估 这群商业性工作者因沙眼衣原体事件 感染和 PID 病例 - 将招募 300 至 600 名女性 估计有 50 至 75 名女性患有 PID 沙眼衣原体，200 名女性患有 PID 将评估无并发症的宫颈衣原体感染的细胞 免疫反应。研究假设 CD4 T 细胞可以保护 对抗沙眼衣原体 PID 和抗原特异性 CD8 T 细胞介导 上生殖道的炎症损伤。蜂窝式 患有 PID 的女性生殖道的免疫反应将 其特点是收集子宫内膜活检组织并确定 浸润子宫内膜的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、CD4 TH1、TH2 和 CD8 CTL。宫颈刮片样本 含有渗出的淋巴细胞也会有细胞因子/酶 确定患有沙眼衣原体的女性 T 细胞亚群的特异性 mRNA 单纯宫颈感染并与患有沙眼衣原体 PID 的女性进行比较。 对于子宫内膜和宫颈样本，RT-PCR 将用于 表征细胞因子/酶 mRNA 模式。总的来说，数据将 揭示 CD8 细胞毒性 T 淋巴细胞在发病机制中的作用 沙眼衣原体 PID 的致病机制以及 CD4 T 的潜在机制 淋巴细胞具有针对沙眼衣原体 PID 的保护作用。