Ikehara S, Kawamura M, Takao F, Inaba M, Yasumizu R, Than S, Hisha H, Sugiura K, Koide Y, Yoshida T O
First Department of Pathology, Kansai Medical University, Osaka, Japan.
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8341-4. doi: 10.1073/pnas.87.21.8341.
Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN mice, which express I-E alpha molecules and have aspartic acid at residue 57 of the I-A beta chain, induced insulitis followed by overt diabetes in the recipient C3H/HeN mice more than 40 weeks after bone marrow transplantation. When cyclosporin A, which perturbs T-cell functions, was injected intraperitoneally into [NOD----C3H/HeN] chimeric mice daily for 1 month, the chimeric mice developed insulitis and overt diabetes within 20 weeks following bone marrow transplantation. Transplantation of bone marrow cells from (NZW x BXSB)F1 mice, which develop lupus nephritis, myocardial infarction, and idiopathic thrombocytopenic purpura, into C3H/HeN or C57BL/6J mice induced in the recipient strains both lupus nephritis and idiopathic thrombocytopenic purpura more than 3 months after transplantation. Transplantation of a stem-cell-enriched population from (NZW x BXSB)F1 mice into normal mice also induced autoimmune disease in the recipients. These results indicate that both systemic autoimmune disease and organ-specific autoimmune disease originate from defects that reside within the stem cells; the thymus and environmental factors such as sex hormones appear to act only as accelerating factors.
将1型糖尿病模型非肥胖糖尿病（NOD）小鼠的骨髓细胞移植到表达I-Eα分子且I-Aβ链第57位残基为天冬氨酸的C3H/HeN小鼠体内，在骨髓移植40周后，受体C3H/HeN小鼠出现胰岛炎，随后发展为明显的糖尿病。当向[NOD→C3H/HeN]嵌合小鼠腹腔内每日注射干扰T细胞功能的环孢素A，持续1个月时，嵌合小鼠在骨髓移植后20周内出现胰岛炎和明显的糖尿病。将患狼疮性肾炎、心肌梗死和特发性血小板减少性紫癜的（NZW×BXSB）F1小鼠的骨髓细胞移植到C3H/HeN或C57BL/6J小鼠体内，在移植3个多月后，受体品系出现狼疮性肾炎和特发性血小板减少性紫癜。将（NZW×BXSB）F1小鼠富含干细胞的群体移植到正常小鼠体内，也会在受体中诱发自身免疫性疾病。这些结果表明，全身性自身免疫性疾病和器官特异性自身免疫性疾病均源于干细胞内存在的缺陷；胸腺和性激素等环境因素似乎仅作为加速因素起作用。
