Highly autoproliferative T cells specific for 60-kDa heat shock protein produce IL-4/IL-10 and IFN-gamma and are protective in adjuvant arthritis

Previously we have shown that T cell responses to the mycobacterial 60-kDa heat shock protein (hsp60) peptide M256-270 mediated protection against adj uvant arthritis in Lewis rats. We have demonstrated now that M256-270-prime d T cells become highly reactive to naive syngeneic APC upon repetitive res timulation in vitro with peptide M256-265, comprising the conserved core of peptide M256-270, These autoproliferative responses in the absence of adde d Ag were MHC class IT restricted and resulted in the production of IL-4/IL -10 and IFN-gamma Enhanced autoproliferation and expression of the cell sur face molecule B7.2 by these T cells were observed in response to syngeneic heat-shocked APC, which indicated that the autoproliferation and expression of B7.2 resulted from the recognition of endogenously expressed and proces sed hsp, Despite their strong autoreactivity, upon transfer such T cells we re found to induce a significant disease reduction in adjuvant arthritis. I n contrast, T cells both primed and restimulated with peptide M256-270 beca me unresponsive toward syngeneic APC as well as toward the conserved core p eptide M256-265, and they were devoid of protective capacity. This study de monstrates that the loss of self-tolerance toward hsp60 does not necessaril y lead to autoimmune disease, but that hsp60-specific self-reactive and aut oproliferative T cells may mediate T cell regulation in arthritis.