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.
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.
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DOI：
10.1084/jem.161.1.72
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发表时间：
1985-01-01
期刊：
影响因子：
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通讯作者：
Masuda T
中科院分区：
文献类型：
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作者：
Sakaguchi S;Fukuma K;Kuribayashi K;Masuda T
器官特异性自身免疫性疾病，如卵巢炎、胃炎、甲状腺炎和睾丸炎，在雌性或雄性裸小鼠（nu/nu）中通过转移nu/+脾细胞诱导，其中特定的Lyt T细胞亚群已被去除：用抗Lyt- 1加补体（C）处理的nu/+脾细胞在受体裸小鼠中引起疾病;相反，抗Lyt-2加C处理的脾细胞不会引起疾病。负责疾病诱导的细胞被认为是Thy-1+、Lyt-1-、2，3-（Thy-1，Lyt-1，2，3），因为用包括抗Lyt-1和抗Lyt-2的混合抗血清加C处理的脾细胞可以以与抗Lyt-1加C处理的细胞几乎相同的发病率诱导疾病（卵巢炎50%，胃炎25%，甲状腺炎10- 20%，睾丸炎40%）。用抗Thy-1、抗Lyt-1和抗Lyt-2的混合抗血清加上C处理的细胞不能诱导自身免疫性疾病。每种诱导的自身免疫性疾病都可以通过脾细胞过继转移到其他裸鼠，导致相应器官的组织学病变和特异性循环自身抗体的产生。由于供体脾细胞的抗Thy-1加C治疗消除了转移疾病的能力，我们得出结论，T细胞是必需的效应细胞，这些细胞可能从Lyt-1-，2，3-细胞发展而来。Lyt-1+，2，3-细胞被证明对疾病的发展具有抑制活性; Lyt-1+，2，3-细胞与Lyt-1-，2，3-细胞的共转移完全抑制了自身免疫的诱导。当抗Lyt-2加C处理的细胞（即，Lyt-1+，2，3-和Lyt-1-，2，3-细胞）与抗Lyt-1和抗Lyt-2加C处理的细胞（即，Lyt-1-，2，3-细胞），然后转移到裸鼠中，即使是小剂量的Lyt-1+，2，3-细胞，也明显抑制了每种自身免疫性疾病的发展。我们能够诱导的自身免疫性疾病在涉及的器官谱、组织病理学特征和相应器官成分（卵母细胞、壁细胞、甲状腺胶体，包括甲状腺球蛋白和精子）的自身抗体的产生方面与人类器官特异性自身免疫性疾病非常相似。（400字处删节）
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)