Thymus and autoimmunity. Transplantation of the thymus from cyclosporin A-treated mice causes organ-specific autoimmune disease in athymic nude mice.
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.
Sakaguchi
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Department of Biophysics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Sakaguchi
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D000818:Animals; D000831:Animals, Newborn; D001327:Autoimmune Diseases / Q000209:etiology* / Q000517:prevention & control; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D005756:Gastritis / Q000209:etiology; D006579:Heterozygote; D007108:Immune Tolerance / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude / Q000276:immunology*; D009869:Oophoritis / Q000209:etiology; D009928:Organ Specificity; D010195:Pancreatitis / Q000209:etiology; D011183:Postoperative Complications / Q000209:etiology*; D013154:Spleen / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D013950:Thymus Gland / Q000276:immunology / Q000637:transplantation*; D013967:Thyroiditis, Autoimmune / Q000209:etiology
D003524:Cyclosporins