BALB/c athymic nu/nu mice spontaneously developed organ-specific (gastritis, thyroiditis, oophoritis, or orchitis) and systemic (arteritis, glomerulonephritis, and polyarthritis) autoimmune diseases when transplanted with neonatal BALB/c thymuses. Transplantation of thymuses from adult BALB/c mice was far less effective in inducing histologically evident organ-specific autoimmune disease in nu/nu mice. Autoimmune disease developed, however, when adult thymuses were irradiated at a T cell-depleting dose before transplantation. Engrafting newborn thymuses into BALB/c mice T cell depleted by thymectomy, irradiation, and bone marrow transplantation produced similar organ-specific autoimmune disease as well, but thymus engrafting into T cell-nondepleted BALB/c mice (i.e., mice thymectomized as adults, but not irradiated) did not, despite the fact that transplanted thymuses grew well in both groups of mice. The mice with organ-specific autoimmune disease produced autoantibodies specific for the respective organ components, such as gastric parietal cells, thyroglobulins, oocytes, or sperm. The thymus-transplanted nu/nu mice also had hypergammaglobulinemia and developed anti-DNA autoantibodies, rheumatoid factors, and immune complexes in the circulation. These results indicate that: (a) the thymus of a murine strain that does not develop spontaneous autoimmune disease can produce pathogenic self-reactive T cells that mediate organ-specific and/or systemic autoimmune diseases; and (b) such self-reactive T cells, especially those mediating organ-specific autoimmune disease, spontaneously expand and cause autoimmune disease when released to the T cell-deficient or -eliminated periphery.
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1 August 1990
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August 01 1990
Thymus and autoimmunity: capacity of the normal thymus to produce pathogenic self-reactive T cells and conditions required for their induction of autoimmune disease.
S Sakaguchi,
S Sakaguchi
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
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N Sakaguchi
N Sakaguchi
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Search for other works by this author on:
S Sakaguchi
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
N Sakaguchi
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1990) 172 (2): 537–545.
Citation
S Sakaguchi, N Sakaguchi; Thymus and autoimmunity: capacity of the normal thymus to produce pathogenic self-reactive T cells and conditions required for their induction of autoimmune disease.. J Exp Med 1 August 1990; 172 (2): 537–545. doi: https://doi.org/10.1084/jem.172.2.537
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