OT-1 mice display minimal upper genital tract pathology following primary intravaginal Chlamydia muridarum infection

Abstract

Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide and leads to serious pathological sequelae in the upper genital tract (UGT) including pelvic inflammatory disease, ectopic pregnancy, and infertility. Several components of the host immune responses have been shown to contribute to the UGT pathology following genital chlamydial infection. We have shown recently that CD8(+) T cells induce the chlamydial UGT pathology via the production of TNF-α. However, those studies did not determine whether the pathology is mediated by bystander or antigen-specific CD8(+) T cells. In this study, we compared chlamydial clearance and UGT pathology in OT-1 transgenic mice and the corresponding C57BL/6J wild-type mice following primary intravaginal Chlamydia muridarum infection. All CD8(+) T cells in the OT-1 mice respond only to the Ova 257-264 peptide and are incapable of responding to other antigenic epitopes including those of Chlamydia. OT-1 mice displayed vaginal chlamydial clearance comparable to the wild-type animals. However, both oviduct and uterine horn pathology were minimal in the OT-1 mice compared with the high degree of pathology observed in the wild-type animals. These results strongly suggest that Chlamydia-specific, not bystander, CD8(+) T cells mediate the UGT pathological sequelae following genital chlamydial infection.

Figure 1

Chlamydial clearance and UGT pathology in OT-1 mice. Groups of OT-1 and C57BL/6J mice were infected intravaginally with 5 × 10 ⁴ IFU of Chlamydia muridarum . (a) Chlamydial shedding was measured at the indicated time-points after inoculation. On day 80 after inoculation, mice were euthanized and genital tract tissues analyzed for oviduct and uterine horn pathology. (b) Representative oviduct and uterine horn dilatation in C57BL/6J mice compared with OT-1 animals. (c) Oviduct and (d) uterine horn dilatation. Each individual marker represents one oviduct or uterine horn, and the mean ± SEM of greatest cross-sectional oviduct diameter or mean ± SEM of the average uterine horn diameters per group of mice also is shown. The number of normal oviducts or uterine horns (numerator) and the total number of oviducts or uterine horns evaluated (denominator) have been indicated in parentheses on the x -axis. *Significant difference in incidence ( P < 0.01, Fisher's exact test) and ^♣ degree ( P < 0.01, Student's t- test) of oviduct or uterine horn dilatation following primary genital C. muridarum infection in C57BL/6J mice vs. OT-1 mice. Results are composite of two independent experiments. The statistical significance holds true when the experiments are analyzed independently.