Ihm S H, Lee K U, Rhee B D, Min H K
Department of Internal Medicine, College of Medicine, Seoul National University, Korea.
Diabetes Res Clin Pract. 1990 Oct;10(2):123-6. doi: 10.1016/0168-8227(90)90033-p.
Multiple injections of low doses of streptozotocin to susceptible strains of mice produce an experimental autoimmune diabetes mellitus. To investigate the possible initial role of macrophages in the development of insulitis, we studied the effect of macrophage-toxic silica administration on the development of in vitro cellular cytotoxic immune response against pancreatic beta-cells. Multiple streptozotocin-treated mice developed hyperglycemia at day 12 and their splenocytes showed cytotoxicity against cultured rat insulinoma cells. Mice given silica and streptozotocin together remained normoglycemic and their splenocytes showed no cytotoxicity. In contrast, in vitro depletion of macrophages from the splenocytes of mice given multiple streptozotocin alone did not abolish the cytotoxicity. These results show that macrophages themselves contribute little to the cellular cytotoxicity, but are necessary for the development of cytotoxic cells. From these results we suggest that there are at least two different steps in the development of insulitis; the presentation of beta-cell autoantigen by macrophages to helper-T cells, followed by the development of beta-cell-specific cytotoxic cells.
对易患糖尿病的小鼠品系多次注射低剂量链脲佐菌素可引发实验性自身免疫性糖尿病。为了研究巨噬细胞在胰岛炎发展过程中可能的初始作用，我们研究了给予巨噬细胞毒性二氧化硅对体外针对胰腺β细胞的细胞毒性免疫反应发展的影响。多次接受链脲佐菌素治疗的小鼠在第12天出现高血糖，其脾细胞对培养的大鼠胰岛素瘤细胞表现出细胞毒性。同时给予二氧化硅和链脲佐菌素的小鼠血糖保持正常，其脾细胞未表现出细胞毒性。相反，仅对多次接受链脲佐菌素治疗的小鼠的脾细胞进行体外巨噬细胞清除，并未消除细胞毒性。这些结果表明，巨噬细胞本身对细胞毒性作用不大，但对于细胞毒性细胞的发育是必需的。从这些结果我们推测，在胰岛炎的发展过程中至少有两个不同的步骤；巨噬细胞将β细胞自身抗原呈递给辅助性T细胞，随后β细胞特异性细胞毒性细胞发育。
