Phelps R G, Daian C, Shibata S, Fleischmajer R, Bona C A
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029-6574.
J Autoimmun. 1993 Dec;6(6):701-18. doi: 10.1006/jaut.1993.1059.
Tight skin (TSK/+) mice develop a cutaneous hyperplasia associated with the occurrence of autoantibodies characteristic for scleroderma. In order to study the role of autoimmunity in the production of skin fibrosis, we conducted adoptive transfer experiments in which bone marrow cells of TSK/pa mice were infused into pa/pa mice littermates. (C57BL/6 pa/pa mice are used to produce heterozygous TSK/pa mice). Our results showed that after a prodromal period of several months, the transfer of bone marrow cells led to skin fibrosis, the presence of autoantibodies, and increased transcription of (alpha 1) collagen I and TGF beta genes. Infusion of enriched B or T cells alone did not cause skin fibrosis but of B cells alone increased autoantibody production. By contrast, transfer of T and B lymphocytes led to earlier mild fibrosis, cellular infiltration and autoantibody production as well as increased transcription of the (alpha 1) collagen gene. Our results strongly demonstrate, for the first time, that immunocompetent cells can play a role in the activation of collagen synthesis leading to skin fibrosis.
紧皮（TSK/+）小鼠会出现与硬皮病特征性自身抗体产生相关的皮肤增生。为了研究自身免疫在皮肤纤维化产生中的作用，我们进行了过继转移实验，即将TSK/pa小鼠的骨髓细胞注入pa/pa小鼠同窝仔（C57BL/6 pa/pa小鼠用于培育杂合TSK/pa小鼠）。我们的结果显示，经过数月的前驱期后，骨髓细胞的转移导致了皮肤纤维化、自身抗体的出现以及α1胶原蛋白I和转化生长因子β基因转录增加。单独注入富集的B细胞或T细胞不会导致皮肤纤维化，但单独注入B细胞会增加自身抗体的产生。相比之下，T淋巴细胞和B淋巴细胞的转移导致更早出现轻度纤维化、细胞浸润和自身抗体产生以及α1胶原蛋白基因转录增加。我们的结果首次有力地证明，免疫活性细胞可在导致皮肤纤维化的胶原合成激活中发挥作用。
