ORGAN-SPECIFIC AND SYSTEMIC AUTOIMMUNE-DISEASES ORIGINATE FROM DEFECTS IN HEMATOPOIETIC STEM-CELLS
ORGAN-SPECIFIC AND SYSTEMIC AUTOIMMUNE-DISEASES ORIGINATE FROM DEFECTS IN HEMATOPOIETIC STEM-CELLS
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DOI：
10.1073/pnas.87.21.8341
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发表时间：
1990-11-01
影响因子：
11.1
通讯作者：
GOOD, RA
中科院分区：
文献类型：
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作者：
IKEHARA, S;KAWAMURA, M;GOOD, RA
将非肥胖型糖尿病（NOD）小鼠和I型糖尿病模型的骨髓细胞移植到表达I- e - α的C3H/HeN小鼠。在i - a - β的57号残基上有天冬氨酸。在骨髓移植后超过40周，受体C3H/HeN小鼠诱导胰岛素，随后出现明显的糖尿病。将干扰t细胞功能的环孢素A腹腔注射到[NOD .fwdarw.]1个月后，骨髓移植后20周内，嵌合小鼠出现胰岛素炎和显性糖尿病。移植（NZW）次骨髓细胞。将发生狼疮性肾炎、心肌梗死和特发性血小板减少性紫癜的BXSB)F1小鼠在移植3个多月后诱导为狼疮性肾炎和特发性血小板减少性紫癜的受体株C3H/HeN或C57BL/6J小鼠。干细胞富集群体的移植（NZW .times）。BXSB)F1小鼠转化为正常小鼠也可诱导受体自身免疫性疾病。这些结果表明，系统性自身免疫性疾病和器官特异性自身免疫性疾病都起源于干细胞内的缺陷；胸腺和性激素等环境因素似乎只起到加速作用。
Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, and model for type I 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 .fwdarw. 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 .times. 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 .times. 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.