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

摘要

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)