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

胸腺最重要的功能是教育T细胞正确识别自我和非我。这一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，我们建立了一种可能基于胸腺细胞间异常或不完全相互作用的多器官局限性自身免疫病模型。我们将15日龄胎鼠的胸腺部分移植到BALB/c裸鼠肾被膜下，以重建T细胞功能。原始细胞发育良好，形成了由供体上皮细胞和宿主淋巴细胞组成的胸腺结构。对SRBC的抗体反应检测表明，间接PFC的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，而来自异基因小鼠和非供体品系的大鼠的皮肤移植被强烈排斥。在常规环境下，TG裸鼠存活没有任何明显的感染性疾病。然而，组织学和免疫荧光研究表明，甲状腺、唾液腺、胃、肾上腺、前列腺、卵巢等多器官局限性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小鼠体内，研究了在该自身免疫模型中效应细胞的极化作用。用单抗进行了荧光激活细胞分选器的阳性选择实验。这些结果表明，大鼠胸腺移植在相当程度上重建了裸鼠的T细胞功能，但器官局限性自身免疫病的发生，可能是由于受体的某些自身抗原被新重组的宿主免疫识别所致。

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.