GENE KNOCKOUT MICE ESTABLISH A PRIMARY PROTECTIVE ROLE FOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-RESTRICTED RESPONSES IN CHLAMYDIA-TRACHOMATIS GENITAL-TRACT INFECTION

Mice with disrupted beta(2)-microglobulin (beta(2)m(-/-)), I-A (class II-/-), or CD4 (CD4(-/-)) genes were examined for their capacity to resolve Chlamydia trachomatis genital tract infection, C57BL/6 and beta(2)m(-/-) mice resolved infection similarly and were culture negative by 4 to 5 weeks following infection, Conversely, major histocompatibility complex (MHC) class II-/- mice failed to resolve infection, and CD4(-/-) mice showed a significant delay (2 weeks), Secondary challenge of C57BL/6, beta(2)m(-/-), and CD4(-/-) mice established that acquired protective immunity, which was characterized by an infection of shortened duration and reduced shedding of infectious organisms, developed. Serological analysis of C57BL/6 and beta(2)m(-/-) mice by enzyme-linked immunosorbent assays revealed no striking differences in the immunoglobulin subclass specificity of the anti-Chlamydia response, although some differences were observed in the magnitude of the immunoglobulin G2a (IgG2a) and IgG2b responses, Class II-/- mice produced lower-titered serum anti Chlamydia antibodies of all isotypes. The serum antibody responses of CD4(-/-) mice were similar to those of C57BL/6 mice, except that the anti-Chlamydia IgA response was delayed by approximately 3 weeks, Analysis of vaginal washes for Chlamydia-reactive antibodies revealed the presence of IgG2a, IgG2b, and IgA in C57BL/6 and beta(2)m(-/-) mice and primarily of IgA in CD4(-/-) mice, Vaginal washes from class II-/- mice were consistently antibody negative, Interestingly, the Chlamydia-specific IgA response in the vaginal washes of CD4(-/-) mice was delayed, but its appearance coincided with decreased shedding of infectious organisms and resolution of infection, Our results demonstrate that MHC class II-restricted T-cell responses are necessary for the development of protective immunity to Chlamydia genital tract infection and that local (vaginal) anti-Chlamydia IgA antibody coincides with the resolution of infection, A substantive role for MHC class I-restricted T-cell responses in protective immunity to Chlamydia genital tract infection was not confirmed.