Studies of T cell-mediated immunity in the human female genital tract (FGT) have been problematic due to difficulties associated with the collection of mucosal samples. Consequently, most studies rely on biopsies from the lower FGT or remnant tissue from hysterectomies with poor cell yields to undergo extensive analysis. Menstruation is the cyclical sloughing off of endometrial tissue and is a source of lymphocytes from the FGT without the need for a biopsy. Our published data and recent data from others in healthy women demonstrated that T cells can be isolated from menstrual blood (MB) and they expressed markers consistent with having homed to a mucosal compartment. Furthermore, MB T cells were functional as determined by antigen-specific intracellular cytokine production assays. In this proposal we want to determine if HIV-1 specific T cells isolated from MB resemble T cells isolated from tissue from the FGT and can be used to study antigen-specific responses in the FGT. This work is important because HIV in women is acquired most frequently via the genital tract, yet our understanding of cell-mediated immunity in this mucosal compartment is lacking. Our studies will determine the types of T cells that are established in the FGT from a local infection and whether systemic immunization to a sexually acquired infection is capable of inducing T cell responses that can be detected in the FGT of healthy women. These data may open new avenues of investigation for cell mediated immune studies involving the FGT that can further the development of vaccination strategies that can induce effective memory T cells that will home and be maintained in the FGT. These studies will also add new information to the study of human mucosal immunology.
Specific Aim 1 will define the phenotypes and functions of HIV-specific T cells from MB of HIV-infected women that distinguish them as a mucosal tissue.
Specific Aim 2 will determine whether antigen-specific T cells localize to the FGT following systemic immunization of HIV-seronegative women. For these studies samples from women immunized with experimental HIV vaccines will be used.
Women are at highest risk for acquiring HIV through sexual exposure and an optimal vaccine needs to generate protective immune responses at the site of infection, mainly the genital tract. Studying vaccine cell-mediated responses in the female genital tract has been difficult, and usually biopsies are needed. This proposal wants to establish menstrual blood as a mucosal tissue to study immunity in the female genital tract.
| Moylan, David C; Goepfert, Paul A; Kempf, Mirjam-Colette et al. (2016) Diminished CD103 (?E?7) Expression on Resident T Cells from the Female Genital Tract of HIV-Positive Women. Pathog Immun 1:371-387 |
