Abstract
BackgroundThe local tissue microenvironment plays an important role in the induction, homing, maintenance and development of effector functions of T cells. Thus, site-specific differences in phenotypes of mucosal and systemic T cell populations have been observed. Chlamydia trachomatis most commonly infects the endocervix in women, yet little is known about Chlamydia-specific effector T cell immunity at this unique mucosal site. Our previous flow-cytometry-based study of cervical-cytobrush retrieved cells indicated that CD8 T cells are significantly increased in the C. trachomatis-infected human endocervix. The cytolytic function of CD8 T cells is important in the protective immunity against many intracellular pathogens, and requires the cytolytic granule perforin to facilitate the entry of other molecules that mediate the lysis of target cells. Determination of perforin expression of the CD8 T cell population in the endocervix would therefore provide insights on the granule-mediated cytolytic potential of these cells at this site.ResultsOur histological data revealed that C. trachomatis-infected tissues have significantly higher numbers of CD3 and CD8 T cells compared to non-infected tissues (p<0.01), and that the majority of CD8+ cells do not express perforin in situ. A subsequent flow cytometric analysis of paired blood and endocervix-derived cells (n=16) revealed that while all the CD8 T cell subsets: naïve, effector memory (TEM), central memory (TCM) and terminally differentiated effector memory (TEMRA) can be found in the blood, the endocervix is populated mainly by the TEM CD8 T cell subset. Our data also showed that perforin expression in the TEM population is significantly lower in the endocervix than in the blood of C. trachomatis positive women (n=15; p<0.0001), as well as in C. trachomatis-negative individuals (n=6; p<0.05). Interestingly, our in vitro co-culture study suggests that the exposure of HeLa 229 cervical epithelial cells to IFN gamma could potentially induce a decrease in perforin content in CD8 TEM cells in the same microenvironment.ConclusionsThe low perforin content of CD8 TEM cells in the endocervix, the local site of C. trachomatis infection in women, may reflect the unique immunological environment that balances immune protection against sexually transmitted infections and immune- tolerance to support conception.
Highlights
The local tissue microenvironment plays an important role in the induction, homing, maintenance and development of effector functions of T cells
CD8 T cells infiltrate the human endocervix during C. trachomatis infection Consistent with our previous findings with cytobrushretrieved endocervical T cells, immunohistological staining for CD3 and CD8 T cell infiltrates in six C. trachomatisnegative and four C. trachomatis-positive banked endocervical tissues demonstrated that the number of CD3+ and CD8+ T cells is significantly higher in C. trachomatispositive than in C. trachomatis-negative endocervical tissues (p
The CD8 T cell repertoire in the human endocervix is distinct from the periphery To further analyze the endocervical immune cell repertoire, we performed multiparameter flow cytometric analyses to determine the mononuclear leukocyte types in isolated peripheral blood mononuclear cells (PBMC) and cytobrush-retrieved endocervical cells from 15 C. trachomatis-infected and 6 uninfected young women attending the Delgado Clinic
Summary
The local tissue microenvironment plays an important role in the induction, homing, maintenance and development of effector functions of T cells. Chlamydia trachomatis most commonly infects the endocervix in women, yet little is known about Chlamydia-specific effector T cell immunity at this unique mucosal site. The cytolytic function of CD8 T cells is important in the protective immunity against many intracellular pathogens, and requires the cytolytic granule perforin to facilitate the entry of other molecules that mediate the lysis of target cells. Determination of perforin expression of the CD8 T cell population in the endocervix would provide insights on the granule-mediated cytolytic potential of these cells at this site. CD8 T cells are key cellular components in the control of many intracellular microbial infections via their cytolytic function. Investigation of the CD8 T cell cytolytic response to C. trachomatis infection is important as it could reveal a mechanism by which the bacterium is deprived of its intracellular niche. Perforin is suggested to be necessary in CD8 T cell cytolytic activity, as perforin deficient mice have reduced efficiency in controlling viral infection [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
