Advisory Committee Chair
William M Geisler
Advisory Committee Members
Robinna G Lorenz
Chad H Steele
Paul A Goepfert
David E Briles
Document Type
Dissertation
Date of Award
2017
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Chlamydia trachomatis (CT) infection is the most prevalent bacterial sexually transmitted infection worldwide and women are disproportionately affected due to its reproductive complications. T cell phenotypes present during CT infection have been well characterized in the murine model, but remain to be elucidated in humans. Therefore, studies aimed at increasing our understanding of T cell phenotypes in CT-infected humans were the focus of this dissertation. The first chapter of this dissertation reviews various aspects of chlamydial infection while in the second chapter aims to address the influence of CT infection on T cell phenotypes. We first compared differences in peripheral blood T cell phenotypes from CT-infected women vs. CT-seronegative controls and found that CT-infected women had higher expression of CD4+ and CD8+ T cell activation markers (CD38 and HLA-DR), CD4+ T helper 1 (Th1)- and Th2-associated effector phenotypes (CXCR3 CCR5 and CCR4), and homing markers (CXCR3 and CCR7, but not CCR5). We then evaluated changes in T cell phenotypes after CT treatment and their association with CT reinfection, comparing peripheral blood T cell phenotypes in CT-infected women at an initial visit (prior to treatment) and follow-up visits (at 3 and 6 months). We found CD4+ and CD8+ T cells had higher expression of activation markers, homing, and Th-2 associated chemokine receptors in their initial visit with active infection versus at the 3-month follow-up visit when infection had cleared, suggesting T cell phenotypes return to a basal state in the absence of infection. We also saw a decrease in same T cells phenotypes in women who became CT reinfected at their first follow-up visit, possibly because of a lower CT load at this visit. Our study also demonstrated that certain T cell phenotypes differ in women with vs. without CT reinfection at follow-up visits, suggesting some phenotypes may be associated with protective immunity. In the third dissertation chapter, we evaluated differences in circulating (peripheral) vs. mucosal T cell phenotypes in CT-infected women. We found a higher proportion of genital mucosal T cells were activated and expressed CCR5 and Th1-associated CKRs compared to peripheral T cells, but a lower proportion of mucosal T cells expressed homing CKR CCR7, Th-2 associated CKR CCR4, and CXCR3+CCR4+ for both T cell subsets. T cell phenotypes differed in the peripheral vs. genital mucosa compartments in CT-infected women. Since CT infects mucosal epithelial cells, finding a higher frequency of activated T cells and Th-1 phenotypes in the mucosa likely reflects an adaptive immune response to infection. Our findings could be useful in understanding adaptive immune mechanisms in human CT infections and aid vaccine development.
Recommended Citation
Ogendi, Brian Makori Omwena, "Evaluation Of Peripheral And Mucosal T Cell Phenotypes Of Chlamydia-Infected Women" (2017). All ETDs from UAB. 2616.
https://digitalcommons.library.uab.edu/etd-collection/2616
