Regulation of immune responses to chlamydial outer membrane proteins

Chlamydia trachomatis cause ocular and genital tract diseases that affect as many as one billion people worldwide. A better understanding of the immune responses induced by these organisms is necessary to develop a Chlamydia vaccine that offers an effective means of disease control. The C. psittaci strain Guinea Pig Inclusion Conjunctivitis (GPIC) provides an excellent model for disease since this natural pathogen of the guinea pig causes both ocular and genital tract infections that closely resemble those caused by C. trachomatis in humans. While many investigators have undertaken the analysis of the mouse immune response to various C. trachomatis proteins, similar studies using GPIC are described here. The chlamydial major outer membrane protein (MOMP) is believed to play a role in protective immunity. The data presented here indicate that when mice are immunized with either whole GPIC elementary bodies (EBs) or recombinant MOMP (rMOMP), the MOMP-specific antibody response is MHC-linked such that mice of the H-2{dollar}sp{lcub}rm d{rcub}{dollar} haplotype are high responders while mice of the H-2{dollar}sp{lcub}rm k{rcub}{dollar} haplotype are low responders. These results have implications for the efficacy of a MOMP-based subunit vaccine. Because the nature of the CD4{dollar}sp+{dollar} T helper (T{dollar}sb{lcub}rm H{rcub}{dollar}) cell response can determine susceptibility or resistance to infection, the stimulation of specific T{dollar}sb{lcub}rm H{rcub}{dollar} subsets in EB-immunized mice was also addressed. In these studies, antibodies specific for the 60-kDa cysteine-rich outer membrane protein (Omp2), induced in all EB-immunized mouse strains, were analyzed. EB-immunized lipopolysaccharide (LPS) responsive BALB/c, BALB.K and C3H/HeSnJ mice produce a mixture of specific IgG{dollar}sb1{dollar} and IgG{dollar}sb{lcub}rm 2a{rcub}{dollar} antibodies. In contrast, the specific antibody response induced in the LPS hyporesponsive C3H/HeJ mouse strain is almost entirely of the IgG{dollar}sb{lcub}rm 2a{rcub}{dollar} isotype characteristic of a {dollar}rm Tsb{lcub}H{rcub}1{dollar}-mediated response. These results indicate that the stimulation of antigen specific T{dollar}sb{lcub}rm H{rcub}{dollar} cell subsets are influenced by LPS. These mice may provide a useful model system in which to investigate the mechanisms involved in the stimulation of antigen-specific {dollar}rm Tsb{lcub}H{rcub}{dollar}1 and {dollar}rm Tsb{lcub}H{rcub}2{dollar} responses and their role in protective immunity and disease pathogenesis.