Chlamydia trachomatis is a major cause of genital tract infections, and in women, these infections often lead to serious complications such as, salpingitis, tubal blockage and infertility. Although immunity to chlamydial infection has been studied for over 20 years, our understanding of the precise role of the immune responses elicited following infection are inadequately defined. Gene targeting has been used to produce mice with disrupted beta2 microglobulin (beta2M-/-), I-A (class II-/-), or CD4 (CD4-/-) genes. These mice are devoid of cell surface expression of MHC class I, MHC class II and CD4 molecules, respectively. Beta2M-/- mice are deficient in CD8+ cytotoxic T lymphocytes, class II-/- mice lack helper T cells (CD4+), and CD4-/- mice have reduced levels of helper T cell activity. In this study we examined the capacity of those immunodeficient mouse strains to resolve Chlamydia trachomatis genital tract infection. C57BL/6 and beta2M-/- mice resolved their infections similarily, and were culture negative by 4 to 5 weeks following infection. However, class II-/- mice failed to resolve infection and CD4+ mice showed a delay (2 weeks) in the resolution of chlamydial genital tract infection. Secondary challenge of beta2M-/- and CD4-/- mice established that acquired immunity developed in these mice, that was characterized by an infection of shortened duration and reduced shedding of infectious chlamydia. Serological analysis of C57BL/6 and beta2M-/- mice by ELISA revealed no striking differences in anti-EB, IgM, IgG1, IgG2a, IghG2b, IgG3 or IgA antibodies, although some differences were observed in the magnitude of the IgG2a and IgG2b responses. Conversely, class II-/- mice produced far less anti-chlamydial antibodies of all isotypes, and CD4-/- mice has antibody responses similar to C57BL/6 mice except the IgA response in CD4-/- animals was delayed and of lower titer. Analysis of vaginal washes for anti-chlamydial antibodies revealed the presence of IgG2a, IgG2b and IgA in C57BL/6 and beta2M-/- mice, chlamydial antibodies in class II-/- mice, and primarily IgA in CD4-/- mice. Furthermore, the appearance of chlamydial-specific IgA in the vaginal wash of CD4-/- was delayed and its appearance coincided with decreased chlamydial shedding and resolution of infection. C57BL/6 and classes II-/-0 mice were tested for chlamydial-specific delayed hypersensitivity responses. Chlamydial specific delayed hypersensitivity was not demonstrated in class II-/- mice. These results clearly demonstrated that MHC class I restricted CD8+ cytotoxic T cells were not required for the resolution of chlamydial genital tract infection. Furthermore, cell surface expression of MHC class II molecules was found to be essential for the development of protective immunity to chlamydial infection, and a strong correlation exists between chlamydial specific IgA in vaginal secretions and recovery from genital tract infection.
