REPEATED CHLAMYDIA-TRACHOMATIS INFECTION OF MACACA-NEMESTRINA FALLOPIAN-TUBES PRODUCES A TH1-LIKE CYTOKINE RESPONSE ASSOCIATED WITH FIBROSIS AND SCARRING

Chlamydia trachomatis-associated female infertility and ectopic pregna ncy are caused by postinflammatory fibrosis and scarring of the upper genital tract, Scarring of the upper genital tract is associated with multiple infectious episodes with C. trachomatis. To study the immune response that occurs with multiple infections of C. trachomatis in the female upper genital tract, a Macaca nemestrina model was used, Subcu taneous pockets containing autologous salpingeal tissue implants were inoculated three times with C. trachomatis. The inflammation after thr ee inoculations was associated with a mononuclear infiltrate dominated by CD8 T-cell lymphocytes, Perforin mRNA was induced in infected pock ets, demonstrating that activated cytolytic lymphocytes were present i n the lesions, Fibrosis, as evidenced by fibroblast proliferation and connective tissue deposition, was observed by the third infection, Cyt okine mRNAs induced by repeated chlamydial infection included gamma in terferon, interleukin-2 (IL-2), IL-6, and IL-IO mRNAs, but IL-4 mRNA w as not induced, Nearly identical findings were found in macaque fallop ian tubes infected in situ repeatedly with C. trachomatis, validating the subcutaneous pocket model of chlamydial salpingitis. However, it w as not possible to evaluate if there was an induction of perforin mRNA in infected salpingeal tubes in situ, because there was a high basal level of perforin mRNA in these tissues, These results suggest that re peated chlamydial infection of the female upper genital tract leads to CD8 T-cell predominance, a Th1-like cytokine milieu, and these inflam matory changes are associated with progression to fibrosis associated with female infertility.