Sakaguchi S, Sakaguchi N
Department of Biophysics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Exp Med. 1988 Apr 1;167(4):1479-85. doi: 10.1084/jem.167.4.1479.
Organ-specific autoimmune diseases such as gastritis, oophoritis, thyroiditis, or insulitis developed in athymic nu/nu mice after engraftment of the thymus from euthymic nu/+ mice treated with cyclosporin A (CsA), a potent immuno-suppressant. The development of autoimmune disease in the nu/nu mice was prevented by inoculation of thymocyte suspensions prepared from normal nu/+ mice, but not by thymocyte suspensions from CsA-treated nu/+ mice. Cotransplantation of normal nu/+ mouse thymus with CsA-treated thymus also suppressed the development of autoimmune disease. Inoculation of spleen cell suspensions prepared from normal adult nu/+ mice prevented autoimmune disease, but inoculation of those from newborn nu/+ mice did not. Thus, CsA appears to interfere selectively with the thymic production of certain suppressor T cells controlling self-reactive (autoimmune) T cells, allowing the latter to expand and cause autoimmune disease.
在移植了用强效免疫抑制剂环孢素A(CsA)处理的正常有胸腺nu/+小鼠的胸腺后,无胸腺nu/nu小鼠会发生器官特异性自身免疫性疾病,如胃炎、卵巢炎、甲状腺炎或胰岛炎。给nu/nu小鼠接种由正常nu/+小鼠制备的胸腺细胞悬液可预防自身免疫性疾病的发生,但接种由CsA处理的nu/+小鼠的胸腺细胞悬液则不能预防。将正常nu/+小鼠胸腺与经CsA处理的胸腺共同移植也可抑制自身免疫性疾病的发展。接种由正常成年nu/+小鼠制备的脾细胞悬液可预防自身免疫性疾病,但接种由新生nu/+小鼠制备的脾细胞悬液则不能预防。因此,CsA似乎选择性地干扰了某些控制自身反应性(自身免疫性)T细胞的抑制性T细胞的胸腺生成,从而使后者得以扩增并引发自身免疫性疾病。