CELLULAR TRAFFICKING TO INFLAMED FEMALE GENITAL MUCOSA

盆腔炎、输卵管不孕和异位妊娠通常出现在女性慢性感染沙眼衣原体或淋病奈瑟菌后。由于衣原体感染的潜伏性，人们已经在努力开发一种疫苗，以加强生物体的清除，避免慢性感染，从而消除生殖残疾。根据共同粘膜免疫系统的理论，当淋巴细胞在远处粘膜表面被激活时，预计淋巴细胞会向生殖器粘膜募集。对小鼠生殖道衣原体感染的研究表明，T细胞需要保护，在其他粘膜部位免疫后，生殖道粘膜中发现了效应T细胞。目前，人类在其他粘膜表面递送抗原后，T细胞迁移到生殖器粘膜的程度尚不清楚。在这个提议中，我们将验证在其他粘膜表面活化的T细胞可以在炎症过程中被招募到生殖器粘膜的假设。由于T细胞不常被招募到生殖器粘膜，我们将研究感染沙眼衣原体或淋病奈瑟菌的女性作为模型来验证这一假设。本提案的具体目标是：1)开发一种方法来识别体内性传播疾病（STD）患者生殖器粘膜的T细胞。2)确定远处粘膜途径的免疫是否促进T细胞运输到生殖器粘膜。我们将使用流式细胞术技术确定归巢受体在性病感染志愿者宫颈内T细胞和ifnγ +外周血细胞上的表达模式（肠粘膜、其他粘膜、非粘膜）。我们还将通过体外输卵管活组织培养和免疫组织学染色来确定在性病感染期间女性生殖器粘膜内诱导了哪些粘附分子。候选归巢受体：粘附分子对将在生殖器粘膜粘附试验中进行测试。在接种伤寒沙门菌疫苗后，通过不同途径监测志愿者生殖器粘膜归巢T细胞和成熟树突状细胞的频率。这些研究将有助于设计在女性生殖器粘膜中提供持久免疫的性病疫苗。

Pelvic inflammatory disease, tubal infertility and ectopic pregnancy typically emerge in females after a chronic infection with Chlamydia trachomatis or Neisseria gonorrhoeae. Due to the insidious nature of chlamydial infections, efforts have been put forth to develop a vaccine that would enhance the clearance of organisms, avoid chronic infections, and in turn, eliminate reproductive disability. Based on the theory of a common mucosal immune system, lymphocyte recruitment to the genital mucosa is predicted to occur when lymphocytes are activated at distant mucosal surfaces. Studies of Chlamydia genital infection in the mouse have shown that T cells are required for protection and effector T cells are found in the genital mucosa following immunization at other mucosal sites. Currently, the degree of T cell migration to the genital mucosa following antigen delivery at other mucosal surfaces is unknown in humans. In this proposal, we will test the hypothesis that T cells activated at other mucosal surfaces can be recruited to the genital mucosa during an inflammatory process. Since T cells are not commonly recruited to the genital mucosa, we will study females infected with C. trachomatis or N. gonorrhoeae as a model to test this hypothesis. The specific aims of this proposal are to: 1) Develop a method to identify T cells that home to the genital mucosa in vivo using individuals with a sexually transmitted disease (STD). 2) Determine if immunization by a distant mucosal route promotes T cell trafficking to the genital mucosa. We will define the homing receptor expression pattern (gut mucosal, other mucosal, non-mucosal) on endocervical T cells and IFNgamma+ peripheral blood cells from STD infected volunteers using flow cytometric techniques. We will also determine which adhesion molecules are induced within the female genital mucosa during STD infection by utilizing an in vitro fallopian tube culture of living tissue followed by immunohistological staining. The candidate homing receptor: adhesion molecule pairs will be tested in a genital mucosa adhesion assay. The frequency of genital mucosa homing T cells and mature dendritic cells will be monitored in volunteers following immunization with Salmonella typhi vaccine via different routes. These studies will contribute to the design of STD vaccines that would provide lasting immunity in the female genital mucosa.