Hutchings P R, Cooke A
Department of Pathology, University of Cambridge, U.K.
Diabetes. 1995 Aug;44(8):906-10. doi: 10.2337/diab.44.8.906.
Soluble bovine or ovine insulin given intravenously to female NOD mice shortly after weaning had a downregulating effect on several autoimmune parameters associated with insulin-dependent diabetes. The titer of spontaneous anti-insulin antibodies was reduced, insulitis was delayed and less severe, and only 25% of treated mice were diabetic at 30 weeks compared with 70% of untreated mice. An interesting paradox occurred in that bovine insulin, although poorly immunogenic in NOD mice and ineffective as a tolerogen for complete Freund's adjuvant-induced cellular and humoral responses to ovine insulin, was nearly as effective as immunogenic ovine insulin in protecting against diabetes and better than ovine insulin at downregulating spontaneous autoantibodies to insulin. Bovine and ovine insulins differ by only one amino acid on the A-chain loop, but whereas modulation of the induced response to ovine insulin appeared to be sheep-specific, modulation of the induced and spontaneous autoimmunity was achieved almost equally well by bovine or ovine insulin. We suggest therefore that modulation of the induced and spontaneous responses are dependent on different T-cell epitopes and that modulation of spontaneous autoimmunity appears to be governed by an epitope common to both insulins.
在雌性非肥胖糖尿病（NOD）小鼠断奶后不久静脉注射可溶性牛胰岛素或羊胰岛素，对与胰岛素依赖型糖尿病相关的几个自身免疫参数具有下调作用。自发抗胰岛素抗体的滴度降低，胰岛炎延迟且程度较轻，与70%未治疗的小鼠相比，30周时只有25%接受治疗的小鼠患糖尿病。出现了一个有趣的矛盾现象，即牛胰岛素在NOD小鼠中免疫原性较差，作为弗氏完全佐剂诱导的对羊胰岛素的细胞和体液反应的耐受原无效，但在预防糖尿病方面几乎与具有免疫原性的羊胰岛素一样有效，并且在下调对胰岛素的自发自身抗体方面比羊胰岛素更好。牛胰岛素和羊胰岛素在A链环上仅相差一个氨基酸，然而，虽然对羊胰岛素诱导反应的调节似乎具有绵羊特异性，但牛胰岛素或羊胰岛素对诱导和自发自身免疫的调节效果几乎相同。因此，我们认为诱导反应和自发反应的调节依赖于不同的T细胞表位，并且自发自身免疫的调节似乎由两种胰岛素共有的一个表位控制。
