Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease.
Open Access
- 1 January 1985
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 161 (1) , 72-87
- https://doi.org/10.1084/jem.161.1.72
Abstract
Organ-specific autoimmune diseases such as oophoritis, gastritis, thyroiditis, and orchitis were induced in female or male nude (nu/nu) mice by the transfer of nu/+spleen cells from which particular Lyt T cell subset(s) had been removed: nu/+spleen cells treated with anti-Lyt-1 plus complement (C) caused disease in recipient nude mice; anti-Lyt-2 plus C-treated spleen cells, in contrast, did not. The cells responsible for disease induction are believed to be Thy-1+, Lyt-1-, 2,3- (Thy-1, Lyt-1, 2,3), since spleen cells treated with mixed antisera, including anti-Lyt-1 and anti-Lyt-2, plus C, could induce the disease with almost the same incidence as anti-Lyt-1 plus C-treated cells (oophoritis 50%, gastritis 25%, thyroiditis 10-20%, and orchitis 40%). Cells treated with mixed antisera of anti-Thy-1, anti-Lyt-1, and anti-Lyt-2, plus C, could not induce autoimmune disease. Each induced autoimmune disease could be adoptively transferred to other nude mice via spleen cells, with resulting histological lesion of corresponding organs and development of specific circulating autoantibodies. Since anti-Thy-1 plus C treatment of donor spleen cells abrogated the capacity to transfer the disease, we conclude that T cells are required as effector cells, and that these may develop from Lyt-1-, 2,3- cells. Lyt-1+, 2,3- cells were demonstrated to have suppressive activity upon the development of the diseases; induction of autoimmunity was completely inhibited by the cotransfer of Lyt-1+, 2,3- cells with Lyt-1-, 2,3- cells. When anti-Lyt-2 plus C-treated cells (i.e., Lyt-1+, 2,3- and Lyt-1-, 2,3- cells) were mixed with anti-Lyt-1 and anti-Lyt-2 plus C-treated cells (i.e., Lyt-1-, 2,3- cells) in various ratios, then transferred to nude mice, the development of each autoimmune disease was clearly inhibited, even by small doses of Lyt-1+, 2,3- cells. The autoimmune disease we were able to induce was quite similar to human organ-specific autoimmune disease in terms of the spectrum of organs involved, histopathological features, and the development of autoantibodies to corresponding organ components (oocytes, parietal cells, thyroid colloid, including thyroglobulin, and sperm).(ABSTRACT TRUNCATED AT 400 WORDS)This publication has 38 references indexed in Scilit:
- Genetic susceptibility to post-thymectomy autoimmune diseases in miceImmunogenetics, 1981
- Immunological circuits: cellular composition.1979
- Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes.The Journal of Experimental Medicine, 1979
- Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains.The Journal of Experimental Medicine, 1978
- Induction of autoimmunity in good and poor responder mice with mouse thyroglobulin and lipopolysaccharide.The Journal of Experimental Medicine, 1977
- APPEARANCE OF NONSPECIFIC SUPPRESSOR T-CELLS DURING INVITRO CULTURE1977
- SUPPRESSION OF IGE ANTIBODY-PRODUCTION IN SJL MICE .2. EXPRESSION OF LY-1 ANTIGEN ON HELPER AND NONSPECIFIC SUPPRESSOR T CELLS1977
- Self-Tolerance Maintained by Active Suppressor MechanismsImmunological Reviews, 1976
- THYROIDITIS IN T CELL-DEPLETED RAT - SUPPRESSION OF AUTOALLERGIC RESPONSE BY RECONSTITUTION WITH NORMAL LYMPHOID-CELLS1976
- Evidence for the clonal abortion theory of B-lymphocyte tolerance.The Journal of Experimental Medicine, 1975