Type I diabetes in NOD mice is not associated with insulin-specific, autoreactive T cells.
In the present study the hypothesis was tested that T cells specific for autologous insulin may be involved in beta cell destruction. Lymphoid cell populations from non-immunized, non-obese diabetic (NOD) mice were investigated for spontaneous T-cell reactivity in vitro to rat insulin (identical to mouse insulin) and to porcine insulin (identical to mouse insulin in the immunogenic part of the A chain loop). No significant T-cell proliferation was detected. In vivo priming of non-diabetic NOD mice with rat insulin in CFA, or of diabetic or non-diabetic NOD mice with porcine insulin failed to elicit insulin-specific T-cell responses upon restimulation in vitro. Lymph node cells from NOD mice primed with porcine insulin and treated with anti-Lyt 2 antibodies and C also failed to show insulin-specific reactivity, indicating that suppression by Lyt 2 cells is not involved in the non-responsiveness observed. In addition to porcine and rat insulin, NOD mice were also non-responders to bovine insulin; however, they responded to equine and ovine insulin and to the oxidized chain B of bovine insulin, the latter showing no cross-stimulation in vitro to any of the intact insulin variants. In conclusion, this study indicates that autologous insulin does not serve as autoantigen in the autoimmune destruction of beta cells.
Hurtenbach
U
U
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Maurer
C
C
D000818:Animals; D001188:Artiodactyla; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006736:Horses; D007114:Immunization; D007328:Insulin / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D051381:Rats; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D007328:Insulin