Antigen-Specific CD8+ T Cells Respond to Chlamydia trachomatis in the Genital Mucosa

Abstract

Following sexual transmission, Chlamydia trachomatis specifically targets genital tract epithelial cells. Because epithelial cells are readily recognized by CD8+ T cells, the response of CD8+ T cells to Chlamydia infection has been explored in a number of studies. It has been shown that CD8+ T cells are present in the genital tracts of mice following C. trachomatis infection, but the specificity of these T cells has remained undefined. To determine whether Chlamydia-specific CD8+ T cells migrate to the genital tract in response to Chlamydia infection, we generated retrogenic mice that express a TCR specific for a Chlamydia-specific T cell Ag CrpA. T cells from the retrogenic mice were transferred into naive recipient animals to increase the frequency of Chlamydia-specific T cells to a level at which they could be tracked during primary infection. We observed that the Chlamydia-specific retrogenic T cells proliferated in lymph nodes draining the genital tract in response to genital infection with C. trachomatis. Furthermore, we found that these cells acquired the ability to produce IFN-γ and migrated into the genital mucosa of the infected mice.

Host-Pathogen Co-Evolution: Chlamydia trachomatis Modulates Surface Ligand Expression in Genital Epithelial Cells to Evade Immune Recognition

“…These results may suggest that genital C. trachomatis serovars do not utilize evasion of CD8+ T cell recognition via MHC class I modulation to the extent that disseminating serovars do. Supporting our observations are reports that chlamydia-specific CD8+ T cells are fully capable of lysing epithelial cells infected with genital serovars of C. trachomatis (Roan and Starnbach 2006;Grotenbreg, Roan et al 2008). Others have noted differences in vitro in the innate immune responses to genital C. trachomatis serovar E and disseminating C. trachomatis serovar L2 infection of HeLa cells (Dessus-Babus, Knight et al 2000).…”

Severe Tryptophan Starvation Blocks Onset of Conventional Persistence and Reduces Reactivation of Chlamydia trachomatis

“…Consequently, reactivation of scattered Chlamydia occurring in vivo might be even slower and less efficient. In the context of an ongoing cytotoxic T-cell-mediated immune response against intracellular bacteria (26), this may give the microbe a substantial disadvantage, promoting its eventual eradication. When the results are taken together, scattered Chlamydia bacteria are characterized by a fundamentally different morphological appearance, arrested early development, an altered transcriptional profile, and an impaired ability to become reactivated compared to persistent RBs.…”

Type I Interferon Signaling Exacerbates Chlamydia muridarum Genital Infection in a Murine Model

“…CD4 T cells play a dominant role in the clearance of Chlamydia muridarum genital infection in the mouse model (20,27,28,37), though some contribution by the CD8 cells has been suggested (17,30). Thus, we sought to determine if the improved clearance of chlamydial infection in IFNAR Ϫ/Ϫ mice was associated with an enhanced chlamydial-specific CD4 T-cell response.…”

“…CD4 T cells play a dominant role in the clearance of Chlamydia muridarum genital infection in the mouse model (20,27,28,37), though some contribution by the CD8 cells has been suggested (17,30). Cytokines and chemokines generated as part of the innate response to infection are the stimuli for recruitment of inflammatory cells, including T cells, to the site of infection.…”