INITIAL ROUTE OF ANTIGEN ADMINISTRATION ALTERS THE T-CELL CYTOKINE PROFILE PRODUCED IN RESPONSE TO THE MOUSE PNEUMONITIS BIOVAR OF CHLAMYDIA-TRACHOMATIS FOLLOWING GENITAL-INFECTION

A Th1-type response develops following vaginal infection with the mous e pneumonitis biovar of Chlamydia trachomatis (MoPn). Since the type o f response, i.e., Th1 versus Th2, can be influenced by factors present during T-cell activation, we examined the effects of different routes of MoPn administration on the cytokine profile and resistance against infection following a MoPn vaginal challenge, A dominant Th1-type cyt okine profile developed in mice given live MoPn via the intranasal, or al, and vaginal routes with ratios of gamma interferon-secreting cells to interleukin 4-secreting cells greater than 10. In contrast, mice i njected subcutaneously produced a Th2-type profile with a gamma interf eron/interleukin 4 ratio of only 0.7, These mice also had significantl y higher anti-MoPn immunoglobulin G1 serum titers, confirming a Th2-ty pe cytokine profile. Exposure of mice to live MoPn, by any route prior to vaginal challenge, resulted in a shortened course of infection. Ho wever, the subcutaneous group resolved the vaginal infection more slow ly, with 60% (6 of 10 mice) of the mice still isolation positive 12 da ys after challenge compared with only 20% of mice given live MoPn by o ther routes. Administration of UV-inactivated MoPn did not provide pro tection against a vaginal challenge, The decreased ability to clear in fection was not associated with a shift in the cytokine profile, since intranasal and oral administration of UV-inactivated MoPn resulted in a predominant Th1-type response. Taken together, these data indicate that the initial route of MoPn administration can direct the type of r esponse produced after a local MoPn infection and thus influence the a bility of the immune response to protect against subsequent infection.