Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes.
NOD mice spontaneously develop insulitis and type 1 diabetes (T1D) mellitus similar to humans. Insulitis without overt disease occurs in the BDC2.5 TCR-transgenic NOD mice that express the rearranged TCR alpha- and beta-chain genes of a diabetogenic T cell clone reactive to an unknown beta cell autoantigen. A previous study identified an extensive panel of peptides that are highly active in stimulating T cells from transgenic BDC2.5 mice in culture. However, none of these peptides cause active disease in NOD and BDC2.5 animals or in NOD recipients of adoptively transferred BDC2.5 T cells following direct immunization in vivo. We show that direct immunization of transgenic BDC2.5 mice causes many BDC2.5 T cells to become activated and apoptotic. Strikingly, soluble peptides administered to recipients of activated, highly pathogenic BDC2.5 T cells results in protection from disease. These results suggest that high affinity peptide analogues of autoimmune epitopes might be useful as therapeutic modulators in active autoimmune disease.
Judkowski
Valeria
V
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Rodriguez
Enrique
E
Pinilla
Clemencia
C
Masteller
Emma
E
Bluestone
Jeffrey A
JA
Sarvetnick
Nora
N
Wilson
Darcy B
DB
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D014612:Vaccines / Q000494:pharmacology*
D001786:Blood Glucose; D010455:Peptides; D014612:Vaccines