infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of -specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4 T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4 and CD8 T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4 TNF-α responses, with frequency and magnitude varying significantly depending on the antigen used. CD4 IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8 T cells. About one-third of TNF-α-producing CD4 T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to infection in women was a CD4 TNF-α response, not CD4 IFN-γ, and a subset of the CD4 TNF-α-positive cells produced a second Th1 cytokine.

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T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38HLA-DR), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3CCR5 and CCR4, respectively), and T cell homing marker (CCR7) for both CD4 and CD8 T cells in CT-infected women. At follow-up after treatment of infected women, there were a lower proportion of CD4 and CD8 T cells expressing these markers. These findings suggest a dynamic interplay of CD4 and CD8 T cells in CT infection, and once the infection is treated, these cell markers return to basal expression levels. In women without reinfection, a significantly higher proportion of CD8 T cells co-expressing CXCR3 with CCR5 or CCR4 at follow-up was detected compared to women with reinfection, suggesting they might play some role in adaptive immunity. Our study elucidated changes in T cell phenotypes during CT infection and after treatment, broadening our understanding of adaptive immune mechanisms in human CT infections.

Problem Differences in circulating (peripheral) and mucosal T cell phenotypes in chlamydia-infected women remain largely unknown. Method of study Thirteen paired mononuclear cell specimens from blood and cervicovaginal lavages collected from chlamydia-infected women were stained and analyzed using ten-color cell surface flow cytometry for T cell distribution, activation status, homing, and T helper (Th)-associated chemokine receptors (CKRs). Results A higher proportion of genital mucosal T cells were activated (CD38+HLA-DR+) and expressed CCR5 and Th1-associated CKR CXCR3+CCR5+ 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. Conclusion T cell phenotypes differed in the peripheral vs. genital mucosa compartments in chlamydia-infected women. Since chlamydia infects mucosal epithelial cells, the finding of a higher frequency of activated T cells and Th-1 phenotypes in the mucosa likely reflects an adaptive immune response to infection.

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