Characterization of lymphocyte response in the female genital tract during ascending Chlamydial genital infection in the guinea pig model.

It is well known that pathology caused by chlamydial infection is associated closely with the host response to the organism and that both innate and adaptive host responses contribute to tissue damage. While it is likely that the organism itself initiates the acute inflammatory response by eliciting cytokine and chemokine production from the host cell, the adaptive response is the result of activation of the cell-mediated immune response. While there are several studies describing the nature of the pathologic response in primate, guinea pig, and murine models, there is less information on the kinetics of the CD4 and CD8 response following primary and challenge infections. In this study, we have quantified by flow cytometry the mononuclear cell response to genital infection with the agent of guinea pig inclusion conjunctivitis in the cervix, endometrium, and oviducts at various times following a primary intravaginal infection and after a challenge infection. Tissues from individual animals were assessed for cells expressing CD4, CD8, or Mac-1 and for B cells. Peak responses of each subset occurred 10 to 14 days after a primary infection. The number of Mac-1-expressing cells in each tissue site was found to be dependent on the size of the inoculating dose of chlamydiae. The responses of each cell type were generally stronger in the cervix than in the upper genital tract. In contrast to the murine model but consistent with the primate models, there were equal numbers of CD4 and CD8 cells present in the infiltrates. Twenty-one days after challenge infection, which was performed 50 days after the primary infection, there was a significant increase in the number of CD4, CD8, and B cells in the oviduct compared to the number of these cells at the same time after a primary infection, providing clear cellular evidence for a cell-mediated immune pathologic response.

Systemic immunization with Hsp60 alters the development of chlamydial ocular disease.

PURPOSE: To determine whether immunization with recombinant Hsp60 would exacerbate ocular pathology on challenge with viable chlamydial elementary bodies. METHODS: Guinea pigs were immunized either subcutaneously with recombinant Hsp60 or both subcutaneously with recombinant Hsp60 and ocularly with attenuated Salmonella typhimurium expressing the guinea pig inclusion conjunctivitis (GPIC) Hsp60 antigen. All animals were challenged in the conjunctiva with the agent of GPIC, and the degree of gross ocular pathology was determined. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody titers to Hsp60 were measured in ocular secretions as a measure of the degree of immunization. RESULTS: In primary and challenge GPIC infection, the degree of gross ocular pathology was lower in the immunized group. The presence of high IgA and IgG antibody titers to Hsp60 in tears suggested that the response may have been modified by the presence of blocking antibodies that either may have removed the antigen quickly or prevented interaction with sensitized T cells. In contrast to subcutaneous immunization, the combined immunization regimen, consisting of subcutaneous recombinant Hsp60 followed by ocular inoculation of the attenuated Salmonella, resulted in no difference in gross pathology after reinfection of guinea pigs with GPIC. CONCLUSIONS: These data indicated that the immunization with Hsp60 did not produce exacerbated disease on challenge with viable organisms; however, the data suggested that the route of administration, form of antigen, or both may be critical in the disease process.