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.