Bergerot I, Fabien N, Maguer V, Thivolet C
INSERM U. 197, Faculté de Médecine, Alexis Carrel, Lyon, France.
Clin Exp Immunol. 1995 Nov;102(2):335-40. doi: 10.1111/j.1365-2249.1995.tb03786.x.
To evaluate the effect of IGF-1 on the autoimmune process of beta cell destruction, permissive non-obese diabetic (NOD) recipients were adoptively transferred with 7 x 10(6) autoreactive T cells from diabetic NOD mice and were administered subcutaneously 10 micrograms rhIGF-1, twice daily for 3 weeks. Administration of rhIGF-1 reduced the final incidence of successful transfers of diabetes observed in only 6/24 mice (25%) versus 12/21 (57%) in control mice. A marked reduction of insulitis during histological analysis of pancreatic glands was also observed. Mice treated with rhIGF-1 had a higher percentage of intact islets (48.6 +/- 12% versus 1.6 +/- 1.1%, P = 0.001) and a lower percentage of infiltrated islets. Islets from rhIGF-1-treated mice had a more intense insulin staining reflecting a higher beta cell mass, but no difference was observed in the amount of insulin content of pancreatic extracts and in the amounts of mRNA transcripts for proinsulin. No difference was also observed in the titres of three islet cell antibody (ICA)-positive sera and in the pattern of A2B5 staining. Some mice developed diabetes and severe islet cell infiltration despite rhIGF-1, thus indicating that some committed T cells were still able to invade the islets and cause beta cell destruction. The percentages of CD4+ and CD8+ T cells in the spleen of experimental mice were similar. To evaluate the effects of rhIGF-1 on cell trafficking in recipient mice, T cells from diabetic NOD Thy-1,2 mice injected into congenic NOD-N Thy-1,1 mice were monitored 3 weeks after adoptive cell transfer. The percentage of Thy-1,2+ T cells was significantly reduced in the spleen (10.8 +/- 1.3% versus 17.2 +/- 3.9%, P = 0.004) of rhIGF-1 treated mice in contrast to the thymus (68.4 +/- 7.9% versus 72.87 +/- 6.2%, P = 0.306), suggesting that rhIGF-1 could influence T cell trafficking to the lymphoid organs. The findings that rhIGF-1 has protective effects in autoimmune diabetes opens new perspectives for future experiments as well as for preventive strategies in human type I diabetes.
为评估胰岛素样生长因子-1（IGF-1）对β细胞破坏自身免疫过程的影响，将来自糖尿病非肥胖糖尿病（NOD）小鼠的7×10⁶个自身反应性T细胞过继转移至受体NOD小鼠，并皮下注射10微克重组人胰岛素样生长因子-1（rhIGF-1），每日两次，共3周。给予rhIGF-1降低了糖尿病成功转移的最终发生率，仅6/24只小鼠（25%）出现糖尿病，而对照小鼠为12/21只（57%）。在胰腺组织学分析中还观察到胰岛炎明显减轻。用rhIGF-1治疗的小鼠完整胰岛的百分比更高（48.6±12%对1.6±1.1%，P = 0.001），浸润胰岛的百分比更低。rhIGF-1治疗小鼠的胰岛胰岛素染色更强，反映β细胞量更高，但胰腺提取物中胰岛素含量及胰岛素原mRNA转录本量未观察到差异。三种胰岛细胞抗体（ICA）阳性血清的滴度及A2B5染色模式也未观察到差异。尽管给予rhIGF-1，一些小鼠仍发生糖尿病和严重的胰岛细胞浸润，这表明一些已活化的T细胞仍能侵入胰岛并导致β细胞破坏。实验小鼠脾脏中CD4⁺和CD8⁺T细胞的百分比相似。为评估rhIGF-1对受体小鼠细胞迁移的影响，在过继细胞转移3周后监测从糖尿病NOD Thy-1,2小鼠注射到同基因NOD-N Thy-1,1小鼠体内的T细胞。与胸腺（68.4±7.9%对72.87±6.2%，P = 0.306）相比，rhIGF-1治疗小鼠脾脏中Thy-1,2⁺T细胞的百分比显著降低（10.8±1.3%对17.2±3.9%，P = 0.004），这表明rhIGF-1可能影响T细胞向淋巴器官的迁移。rhIGF-1在自身免疫性糖尿病中有保护作用这一发现为未来实验以及人类I型糖尿病的预防策略开辟了新的前景。
