INSULIN IMMUNIZATION OF NONOBESE DIABETIC MICE INDUCES A PROTECTIVE INSULITIS CHARACTERIZED BY DIMINISHED INTRAISLET INTERFERON-GAMMA TRANSCRIPTION
INSULIN IMMUNIZATION OF NONOBESE DIABETIC MICE INDUCES A PROTECTIVE INSULITIS CHARACTERIZED BY DIMINISHED INTRAISLET INTERFERON-GAMMA TRANSCRIPTION
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DOI：
10.1172/jci117707
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发表时间：
1995-02-01
影响因子：
15.9
通讯作者：
MACLAREN, N
中科院分区：
文献类型：
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作者：
MUIR, A;PECK, A;MACLAREN, N
我们先前报道了每天注射低精蛋白胰岛素预防非肥胖糖尿病（NOD）小鼠的高血糖症和胰岛炎（Atkinson，M.，N. Maclaren;和R.鲁切塔1990.糖尿病39：933-937）。可能的机制包括来自“β-细胞静息”的胰腺β-细胞的免疫原性降低和诱导的对胰岛素的主动免疫调节（Aaen，K.，J. Rygaard，K. Josefsen，H.彼得森角H.布罗格伦，T。Horn和K.布沙尔1990.糖尿病39：697-701）。我们在这里报告，间歇性免疫接种胰岛素或其代谢不活跃的B链在不完全弗氏佐剂也可以预防糖尿病NOD小鼠，而免疫接种A链胰岛素或BSA没有。B链胰岛素免疫小鼠脾细胞的连续转移可预防与致糖尿病脾细胞共输注的受体的糖尿病，这种作用可通过预先体内消除CD 4+或CD 8+细胞而消除。胰岛素免疫并没有减少胰岛内炎症（胰岛炎）的程度，但是，它确实消除了胰岛炎病变内IFN-γ mRNA的表达。因此，胰岛素免疫诱导对B链上决定簇的主动抑制反应，将胰岛炎病变从破坏性转变为保护性。
We reported previously that daily injections of isophane insulin prevented both hyperglycemia and insulitis in nonobese diabetic (NOD) mice (Atkinson, M., N. Maclaren; and R. Luchetta. 1990. Diabetes. 39:933-937). The possible mechanisms responsible include reduced immunogenicity of pancreatic beta-cells from ''beta-cell rest'' and induced active immunoregulation to insulin (Aaen, K., J. Rygaard, K. Josefsen, H. Petersen, C. H. Brogren, T. Horn, and K. Buschard. 1990. Diabetes. 39:697-701). We report here that intermittent immunizations with insulin or its metabolically inactive B-chain in incomplete Freund's adjuvant also prevent diabetes in NOD mice, whereas immunizations with A-chain insulin or with BSA do not. Adoptive transfer of splenocytes from B-chain insulin-immunized mice prevented diabetes in recipients co-infused with diabetogenic spleen cells, an effect that was abolished by prior in vivo elimination of either CD4+ or CD8+ cells. Insulin immunization did not reduce the extent of intraislet inflammation (insulitis); however, it did abolish expression of IFN-gamma mRNA within the insulitis lesions. Immunizations with insulin thus induce an active suppressive response to determinants on the B-chain that converts the insulitis lesion from one that is destructive to one that is protective.