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

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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.