Immunologic effects of human peripheral and intrathyroidal lymphocytes on xenotransplanted human thyroid tissue in athymic nude mice

T cells are intimately involved in the etiology and pathogenesis of human a utoimmune thyroid disease. In order to further elucidate the immunologic me chanisms leading to Craves' disease (GD), we investigated the effects of hu man lymphocytes derived from patients with autoimmune and nonautoimmune thy roid diseases on human thyroid tissue xenotransplanted into nude mice. Eigh t weeks after transplantation of thyroid tissue from 26 patients with nonau toimmune thyroid disease (nontoxic nodular goiter [NTG]) into nude mice, pe ripheral (PBL) and intrathyroidal lymphocytes (ITL) from 14 patients with N TG and 12 patients with GD were engrafted into the animals. ITL and PBL sub sets were analyzed by flow cytometer before engraftment. Two days after lym phocyte engraftment, the thyroid transplants were examined histologically ( HE) as well as immunohistologically by staining with monoclonal antibodies directed against CD3 (T-cell activation and signal transduction), immunoglo bulin G (IgG), HLA class II and CD31 (human endothelium). After injection of GD lymphocytes, thyroid transplants contained significan tly more CD3, HLA class II, and CD4 expressing cells. Engrafted PBL and esp ecially ITL from patients with CD specifically migrated into human thyroid transplants but not into the mouse thyroids, induced expression of class II products and led to IgG production by plasma cells. Persistence of human e ndothelium has been proven by positive CD31 staining, In conclusion, our da ta demonstrate that an organ-specific immune response is induced only by GD lymphocytes that migrate specifically into the thyroid transplants. Persis tence of human endothelial cells in the transplants suggests that homing in this in vivo model reflects the situation in CD patients.