T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides

T cell responses to peptide epitopes of the 60 kDa heat shock protein (hsp6 0) have been shown to play a role in the pathogenesis of type 1 insulin-dep endent diabetes mellitus (IDDM) in mice. To test whether hsp60 autoimmunity might be involved in human type 1 diabetes, we studied T cell proliferativ e responses (stimulation index; SI) to intact human hsp60, to hsp60 peptide s and to a recall antigen (tetanus toroid) in 25 newly diagnosed type 1 dia betes patients, in 22 type 2 (non-insulin-dependent diabetes mellitus, NIDD M) patients, and in 25 healthy blood donors. There were no significant diff erences between the T cell responses of the three groups to tetanus toroid. However, the responses to hsp60 of the type 1 diabetes group (median SI=5) were significantly greater (P<0.01) than those of the type 2 group (median SI=1.67) and of the blood donors (median SI=1.7). Epitope mapping revealed significant responses to at least seven different peptides, with prevalent responses to the p277 peptide previously mapped in NOD mice and to peptide p32. Thus, newly diagnosed type 1 diabetes patients, similar to prediabeti c and newly diabetic NOD mice, show heightened autoimmunity to hsp60 and hs p60 peptides. (C) 1999 Academic Press.