Analysis of multiple organ-localized autoimmune diseases in nude mice grafted with rat thymic rudiment

胸腺最重要的功能是培养T细胞，使其正确识别自我和非自我。这种功能的基础被认为与胸腺上皮细胞和T细胞前体之间的和谐相互作用有关。自身免疫性疾病的发病机制尚未确定。最近，我们建立了一个多器官局限性自身免疫性疾病的模型，可能基于胸腺中异常或不完全的细胞间相互作用。我们将15日龄大鼠的胸腺雏形移植到BALB/c裸鼠的肾亚囊（TG裸）中，重建T细胞功能。幼体发育良好，形成由供体上皮细胞和宿主淋巴细胞组成的胸腺结构。对SRBC抗体反应的检查显示，观察到的间接pfc数量约为正常数量的一半。同种BALB/c小鼠和胸腺供体大鼠的皮肤移植被接受，异体小鼠和其他供体大鼠的皮肤移植被强烈排斥。TG裸鼠在常规环境下无明显感染性疾病。然而，组织学和免疫荧光研究显示，在产生相应自身抗体的小鼠中，甲状腺、唾液腺、胃、肾上腺、前列腺、卵巢和睾丸等多器官局部自身免疫性疾病的发生率很高。通过将病变过继转移到同基因BALB/c nu/nu小鼠中，研究了该自身免疫模型中的效应细胞酰化。采用单克隆抗体荧光活化细胞分选仪进行阳性选择实验。L3T4细胞能诱导病变，而LYt-2^+细胞不能。这些结果表明，大鼠胸腺移植物在很大程度上重建了裸鼠的T细胞功能，但可能由于受体的某些自身抗原被新重建的宿主免疫识别，导致器官局限性自身免疫性疾病的发生。

The most important function of the thymus is education of T cells which properly recognize self and non-self.The basis of this function is thought to link to harmonious interaction between the thymic epithelial cells and T cell precursors.Pathogenesis of autoimmune disease has not been established so for. Recently we developed a model of multiple organ-localized autoimmune diseases probably based on abnormal or incomplete cell-to-cell interactions in the thymus.We transplanted thymic rudiments from 15-day-/ld embryonic rats to renal subcapsule of BALB/c nude mice(TG nude)for reconstitution of T cell function. The rudiments developed well and formed a proper thymus structure composed of donor epithelia and host lymphocytes.Examination of antibody responses to SRBC revealed that approximately of half the normal number of indirect PFCs were observed.Skin grafts from syngeneic BALB/c mice and thymic donor rat strains were accepted,whereas those from allogeneic mice and the rats of other than donor strains were vigorously rejected.The TG nude mice survived without any evident infectious diseases umder a conventional environment.Histological and immunofluorescence studies,however,showed a high incidence of multiple organ-localized autoimmune diseases in thyroid,salivary gland,stomach,adrenal,prostate,ovary, and testis in mice that produced the corresponding autoantibodies.The effector cell popylation in this autoimmune model was studies by adoptive transfer of the lesions into syngeneic BALB/c nu/nu mice.Positive selection experiments by fluorescence-activated cell sorter with monoclonal antibodies were carried out.L3T4 cells,but not LYt-2^+ cells,were capable of inducing lesions. These results together suggested that rat thymic grafts reconstituted T cell functions of nude mice to a considerable degree,but that organ-localized autoimmune diseases developed,probably because certain auto-antigens of the recipients were recognized by the newly reconstituted host immunity.