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 (hsp60) have been shown to play a role in the pathogenesis of type 1 insulin-dependent diabetes mellitus (IDDM) in mice. To test whether hsp60 autoimmunity might be involved in human type 1 diabetes, we studied T cell proliferative responses (stimulation index; SI) to intact human hsp60, to hsp60 peptides and to a recall antigen (tetanus toxoid) in 25 newly diagnosed type 1 diabetes patients, in 22 type 2 (non-insulin-dependent diabetes mellitus, NIDDM) patients, and in 25 healthy blood donors. There were no significant differences between the T cell responses of the three groups to tetanus toxoid. 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 prediabetic and newly diabetic NOD mice, show heightened autoimmunity to hsp60 and hsp60 peptides.
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
R
R
Abulafia-Lapid
D
D
Elias
I
I
Raz
Y
Y
Keren-Zur
H
H
Atlan
I R
IR
Cohen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics; D016022:Case-Control Studies; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000276:immunology; D018604:Epitope Mapping; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D018834:Chaperonin 60; D010446:Peptide Fragments