Hurtenbach U, Maurer C
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
J Autoimmun. 1989 Apr;2(2):151-61. doi: 10.1016/0896-8411(89)90151-0.
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.
在本研究中，对自体胰岛素特异性T细胞可能参与β细胞破坏这一假说进行了验证。对来自未免疫的非肥胖糖尿病（NOD）小鼠的淋巴细胞群体进行体外研究，观察其对大鼠胰岛素（与小鼠胰岛素相同）和猪胰岛素（在A链环的免疫原性部分与小鼠胰岛素相同）的自发T细胞反应性。未检测到明显的T细胞增殖。用弗氏完全佐剂（CFA）中的大鼠胰岛素对非糖尿病NOD小鼠进行体内致敏，或用猪胰岛素对糖尿病或非糖尿病NOD小鼠进行体内致敏，在体外再次刺激时均未能引发胰岛素特异性T细胞反应。用猪胰岛素致敏并用抗Lyt 2抗体和C处理的NOD小鼠的淋巴结细胞也未显示出胰岛素特异性反应性，这表明Lyt 2细胞的抑制作用与所观察到的无反应性无关。除猪胰岛素和大鼠胰岛素外，NOD小鼠对牛胰岛素也无反应；然而，它们对马胰岛素和羊胰岛素以及牛胰岛素的氧化B链有反应，后者在体外对任何完整的胰岛素变体均无交叉刺激作用。总之，本研究表明自体胰岛素在β细胞的自身免疫性破坏中不作为自身抗原。
