MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II REGION CONFERS SUSCEPTIBILITY TO STAPHYLOCOCCUS-AUREUS ARTHRITIS

The importance of the MHC class II region for the development of septi c arthritis was studied in a murine model of haematogenously induced S taphylococcus aureus arthritis. In the first experiment MHC class II d eficient mice (A beta(-/-)) and their heterozygous (A beta(+/-)) litte rmates were intravenously inoculated with a single dose of toxic shock syndrome toxin-1 producing S. aureus LS-1 strain. The results demonst rate that the expression of class II MHC molecules increases the preva lence and severity of arthritis. To analyse the impact of MHC class II haplotypes on the disease onset and progression the authors used cong enic C3H.NB, C3H.Q and C3H/HeJ mice in the second set of experiments. The results show that C3H/HeJ mice developed the highest frequency and the most severe course of arthritis compared with C3H.NB and C3H.Q an imals. Immunohistochemical analysis of arthritic joints revealed equal number of macrophages, CD4(+) and CD8(+) lymphocytes in the inflamed synovia in all the congenic mice. In contrast, the number of MHC class II expressing cells was higher in the arthritic joints of C3H/HeJ mic e compared with the congenic strains (P < 0.001). Furthermore, serum l evels of proarthrtitogenic cytokines, such as tumour necrosis factor a nd interleukin-6 were higher in C3H/HeJ group. This study indicates th at MHC class II expression is necessary for the development of S. aure us arthritis in mice and that different MHC class II haplotypes confer varying susceptibility for development of joint inflammation induced by staphylococci.