Cytotoxic T-cell Mediated Immunity to Chlamydia

性状（由申请方提供）：专性胞内病原体 沙眼衣原体是性传播疾病最常见的原因 在发达国家，导致显性疾病和不孕不育， 全球可预防失明的主要原因。梭菌感染 沙眼导致针对该生物体的特异性免疫应答，并且 CD8+细胞毒性T淋巴细胞（CTL）对C.可以培养沙眼 感染的老鼠。将培养的CD8 + T细胞连续转移到感染的 小鼠减少了这些动物脾脏中的微生物数量。的 在这个提议中的实验旨在确定衣原体基因 产物被这些衣原体特异性鼠CD8 + T细胞识别。三 将使用独立的方法来鉴定这些抗原。一旦C. 负责引发CD8 + T细胞应答的沙眼衣原体基因产物是 确定，他们将被引入到牛痘病毒和测试其 在疫苗策略中刺激保护性T细胞的能力。 由于这些抗原刺激CD8 + T细胞，这表明它们具有免疫原性。 在C.发育性沙眼 周期表征发育调节和亚细胞的实验 这些蛋白质的定位将作为第一步进行， 了解这些蛋白质在C.沙眼发病机制 其他实验将重点关注CD 8 + T细胞的机制 防止衣原体感染。干扰素-g（IFN-g）似乎是 这些T细胞用于保护免受C的主要效应机制。 沙眼感染CD8 + T细胞释放的IFN-g可以保护小鼠免受 C.沙眼感染通过刺激抗微生物活性 巨噬细胞或直接抑制C.沙眼 阐明T细胞产生IFN-γ的机制的实验 介导的保护将使用辐射骨髓嵌合体， 造血细胞（包括巨噬细胞）或驻留细胞不能 由于干扰素-g受体基因的破坏而对干扰素-g产生应答。一 更好地了解对C.沙眼和 疫苗的开发将对世界范围内的发病率产生显著影响， 由这些感染引起的。

DESCRIPTION (provided by the applicant): The obligate intracellular pathogen Chlamydia trachomatis is the most common cause of sexually transmitted disease in the developed world, causing both overt disease and infertility, and is also the leading cause of preventable blindness worldwide. Infection with C. trachomatis results in a specific immune response against the organism, and CD8+ cytotoxic T-lymphocytes (CTL) specific for C. trachomatis can be cultured from infected mice. Adoptive transfer of cultured CD8+ T-cells into infected mice reduces the number of organisms found in the spleens of these animals. The experiments in this proposal are designed to determine which Chlamydia gene products are recognized by these Chlamydia specific murine CD8+ T-cells. Three independent approaches will be used to identify these antigens. Once the C. trachomatis gene products responsible for priming the CD8+ T-cell response are identified, they will be introduced into vaccinia virus and tested for their ability to stimulate protective T-cells in a vaccine strategy. Because these antigens stimulate CD8+ T-cells, it suggests that they have access to the cytosol of host cells during the C. trachomatis developmental cycle. Experiments to characterize the developmental regulation and subcellular localization of these proteins will be carried out as a first step in understanding the role these proteins may play in C. trachomatis pathogenesis. Additional experiments will focus on the mechanism by which CD8+ T-cells protect against Chlamydia infection. Interferon-g (IFN-g) appears to be the primary effector mechanism used by these T-cells to protect against C. trachomatis infection. IFN-g release by CD8+ T-cells could protect mice against C. trachomatis infection by stimulating the antimicrobial activity of macrophages or by directly inhibiting the replication of C. trachomatis. Experiments to clarify the mechanism by which IFN-g produced by T-cells mediates protection will use radiation bone marrow chimeras in which either the hematopoietic cells (including macrophages) or the resident cells are unable to respond to IFN-g as a result of a disruption in the IFN-g receptor gene. A better understanding of the immune response to C. trachomatis and the development of a vaccine would have a pronounced effect on worldwide morbidity resulting from theseinfections.