CELLULAR TRAFFICKING TO INFLAMED FEMALE GENITAL MUCOSA

盆腔炎、输卵管不孕和异位妊娠通常发生在女性慢性感染沙眼衣原体或淋病奈瑟菌后。 由于衣原体感染的隐蔽性，已经努力开发一种疫苗，以加强生物体的清除，避免慢性感染，从而消除生殖残疾。 基于共同粘膜免疫系统的理论，预测当淋巴细胞在远处粘膜表面被激活时，淋巴细胞向生殖器粘膜的募集发生。 对小鼠生殖器衣原体感染的研究表明，T细胞是保护所必需的，在其他粘膜部位免疫后，在生殖器粘膜中发现了效应T细胞。 目前，在人类中，在其他粘膜表面处的抗原递送之后T细胞迁移到生殖器粘膜的程度是未知的。 在这个建议中，我们将测试的假设，在其他粘膜表面激活的T细胞可以在炎症过程中招募到生殖器粘膜。 由于T细胞通常不被募集到生殖器粘膜，我们将研究感染C。trachomatis或N.淋病作为模型来检验这一假设。 该提案的具体目的是：1）开发一种方法，以识别T细胞的家生殖器粘膜在体内使用的个人与性传播疾病（STD）。 2)确定通过远距离粘膜途径免疫是否促进T细胞运输到生殖器粘膜。 我们将使用流式细胞术技术定义性病感染志愿者宫颈内T细胞和IFNgamma+外周血细胞上的归巢受体表达模式（肠道粘膜、其他粘膜、非粘膜）。我们还将确定哪些粘附分子在STD感染期间通过利用活组织的体外输卵管培养物随后进行免疫组织学染色在女性生殖器粘膜内诱导。 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检测。 将在志愿者中通过不同途径接种伤寒沙门氏菌疫苗后监测生殖器粘膜归巢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力的STD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.