In several animal models of rheumatoid arthritis (RA), T cell responses to self 60-kD heat-shock protein 60 (hsp60) protect against the induction of arthritis. The nature of this suppressive T cell activity induced by self hsp60 is not clear. In the present study, T cell responses 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 bacterial 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 cells stimulated with human hsp60 produced significantly lower amounts of IFN-gamma and higher amounts of IL-4 than SF T cells stimulated with bacterial hsp60 (P </= 0.002 and 0.05, respectively), and consequently a lower T1/T2 cell cytokine ratio was observed for human versus bacterial hsp60 (P </= 0.004). Additionally, human and not mycobacterial hsp60-specific T cell lines suppressed TNF-alpha production. Together, our results suggest that human hsp60, as overexpressed in inflamed synovium of patients with RA, can contribute to suppression of arthritis by the stimulation of regulatory suppressive T cell activity.