Expression of mammalian 60-kD heat shock protein in the joints of mice with pristane-induced arthritis.

ABSTRACT

Previous work has indicated that autoimmunity to the mammalian 60-kD heat shock protein (hsp60) may be necessary for the development of pristane-induced arthritis (PIA), a murine model of rheumatoid arthritis. To characterize the expression of hsp60 in murine joints, immunoblots of joint extracts and frozen histological sections prepared from normal or arthritic mice were probed with the hsp60-specific MoAb 4B989. Hsp60 could be detected in the joints of mice with PIA by both techniques, and was seen to be localized within the inflamed pannus using immunhistochemistry. Immunoblotting revealed that lower concentrations of hsp60 are also present in normal mouse joints, and that the level of expression increases with age, in parallel with greater susceptibility to PIA. In other studies, it was demonstrated that the titres of serum IgG antibodies reactive with the related mycobacterial hsp65, and the in vitro responsiveness of splenic T cells to hsp65, are both elevated in older mice. It is considered that the results are consistent with the hypothesis that PIA develops following environmental priming with mycobacterial hsp65, and the targeting of cross-reactive T cells to self-hsp60 in the joints.