Prevention of diabetes in the NOD mouse by a Th1 clone specific for a hsp60 peptide.
Peptide-based therapies have been shown to be effective in the prevention of diabetes in the NOD mouse. We have been interested in the T cell response elicited by such therapies and have been studying a T cell clone (C3.5) specific for hsp60 AA 437-460, generated following immunization with the hsp60 437-460 peptide. The C3.5 clone was CD4(+), Vbeta8.3 TCR(+), I-A(g7)restricted and of the Th1 type. The injection of this clone into prediabetic NOD mice prevented the adoptive transfer of the disease and suppressed the development of spontaneous diabetes. This effect was reflected in a reduction in the degree and severity of insulitis in mice injected with this clone. In addition, an antibody response was elicited to the C3.5 clone in mice given multiple injections of the clone. The epitope recognized by C3.5 is located in the N-terminus of the hsp60 AA 437-460 peptide, and this clone was unable to recognize the native hsp60 molecule. These data raise questions concerning the mechanism by which peptide-based therapies prevent autoimmune disease.
Feili-Hariri
M
M
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Frantz
M O
MO
Morel
P A
PA
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D000939:Epitopes / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D018834:Chaperonin 60; D000939:Epitopes; D010446:Peptide Fragments