Genital tract infection with Chlamydia trachomatis fails to induce protective immunity in gamma interferon receptor-deficient mice despite a strong local immunoglobulin A response

CD4(+) T cells have been found to play a critical role in immune protection against Chlamydia trachomatis infection. Since both humoral and cell-mediated antichlamydial immunity have been implicated in host protection, the crucial effector functions provided by the CD4(+) T cells may rely on Th1 or Th2 functions or both. In the present study, we evaluated the development of natural immunity following vaginal infection with C. trachomatis serovar D in female gamma interferon receptor-deficient (IFN-gamma R(-/-)) mice with a disrupted Th1 effector system, We found that in comparison with wild-type mice, the IFN-gamma R(-/-) mice exhibited a severe ascending primary infection of prolonged duration which stimulated almost 10-fold-stronger specific local immunoglobulin A (IgA) and IgG responses in the genital tract, Following resolution of the primary infection and despite the augmented antibody responses to chlamydiae, the IFN-gamma R(-/-) mice were completely unprotected against reinfection, suggesting that local antibodies play a subordinate role in host protection against chlamydial infection. Immunohistochemical analysis of frozen sections of the genital tract revealed many CD4(+) T cells in the IFN-gamma R(-/-) mice, with a dominance of interleukin 4-containing cells in mice following resolution of the secondary infection, However, in contrast to the Endings with wild-type mice, the typical clusters of CD4(+) T cells were not found in the IFN-gamma R(-/-) mice. Few and similarly distributed CD8(+) T cells were observed in IFN-gamma R(-/-) and wild-type mice, Whereas chlamydia-infected macrophages from wild-type mice had no inclusion bodies (IB) and produced significant amounts of nitric oxide (NO) in the presence of IFN-gamma, macrophages from IFN-gamma R(-/-) mice contained many IB but no NO. These results indicate that CD4(+) Th1 cells and IFN-gamma, rather than local antibodies, are critical elements in host immune protection stimulated by a natural ascending C. trachomatis infection in the female genital tract.