The effort to develop vaccines that can elicit mucosal immune responses in the female reproductive tract (FRT) against sexually transmitted infections (STI) have been hampered by an inability to accurately measure immune responses in the genital tract. Vaccines against STIs should generate localized memory responses at sites of potential exposure to provide better control of infection. Critically, lymphocytes isolated from the genital tract will migrate back into the FRT when transferred into a naïve recipient. Yet, the repertoire of trafficking molecules expressed on cells that will home to FRT is still unknown. The hypothesis of this project is that lymphocytes induced by FRT immunization traffic transiently in blood expressing a specific set of homing markers, but are selectively retained in the FRT after transmigration. By isolating cells from blood shortly after mucosal FRT immunization in animal models and FRT-mucosal infection in patients, we will be able to detect the potential specific integrins and homing receptors responsible for lymphocyte entry into the FRT. The goal is to identify specific integrins and homing receptors expressed on circulating T and B lymphocytes that direct their migration to the female reproductive tract during the brief period in which mucosal lymphocytes re-circulate. Direct comparison of gene and protein expression profiles using microarrays and mass spectrometry technology on subsets of purified peripheral blood will be performed in patients and murine models. Differentially expressed candidate molecules selected from these functional genomic analyses will be confirmed and validated in patients and by competitive homing assays in vivo in mice. Identifying the profile characteristic of lymphocytes migrating to the FRT soon after vaccination or infection will have a critical impact on the detection of recent exposure to a sexually transmitted pathogen and on the development of new STI vaccines.
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