STIMULATION OF SUPPRESSIVE T-CELL RESPONSES BY HUMAN BUT NOT BACTERIAL 60-KD HEAT-SHOCK-PROTEIN IN SYNOVIAL-FLUID OF PATIENTS WITH RHEUMATOID-ARTHRITIS

In several animal models of rheumatoid arthritis (RA), T cell response s to self 60-kD heat-shock protein 60 (hsp60) protect against the indu ction of arthritis, The nature of this suppressive T cell activity ind uced by self hsp60 is not clear, In the present study, T cell response s to human (self) hsp60 in RA in terms of type 1 (T1) and type 2 (T2) T cell activity were assessed, The results show that human and not bac terial hsp60-reactive synovial fluid (SF) T cells of patients with RA proliferate in the presence of the T2 cell growth factor IL-4, SF T ce lls stimulated with human hsp60 produced significantly lower amounts o f IFN-gamma and higher amounts of IL-4 than SF T cells stimulated with bacterial hsp60 (P less than or equal to 0,002 and 0.05, respectively ), and consequently a lower T1/T2 cell cytokine ratio was observed for human versus bacterial hsp60 (P less than or equal to 0.004), Additio nally, human and not mycobacterial hsp60-specific T cell lines suppres sed TNF-ol production, Together, our results suggest that human hsp60, as overexpressed in inflamed synovium of patients with RA, can contri bute to suppression of arthritis by the stimulation of regulatory supp ressive T cell activity.