Highly Autoproliferative T Cells Specific for 60-kDa Heat Shock Protein Produce IL-4/IL-10 and IFN-  and Are Protective in Adjuvant Arthritis (original) (raw)

2000, The Journal of Immunology

Previously we have shown that T cell responses to the mycobacterial 60-kDa heat shock protein (hsp60) peptide M256 -270 mediated protection against adjuvant arthritis in Lewis rats. We have demonstrated now that M256 -270-primed T cells become highly reactive to naive syngeneic APC upon repetitive restimulation in vitro with peptide M256 -265, comprising the conserved core of peptide M256 -270. These autoproliferative responses in the absence of added Ag were MHC class II restricted and resulted in the production of IL-4/IL-10 and IFN-␥. Enhanced autoproliferation and expression of the cell surface 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 processed hsp. Despite their strong autoreactivity, upon transfer such T cells were found to induce a significant disease reduction in adjuvant arthritis. In contrast, T cells both primed and restimulated with peptide M256 -270 became unresponsive toward syngeneic APC as well as toward the conserved core peptide M256 -265, and they were devoid of protective capacity. This study demonstrates that the loss of self-tolerance toward hsp60 does not necessarily lead to autoimmune disease, but that hsp60-specific self-reactive and autoproliferative T cells may mediate T cell regulation in arthritis.

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