EFFECT OF GRAVES-DISEASE INTRATHYROIDAL LYMPHOCYTES (ITL) ON XENOTRANSPLANTS OF HUMAN THYROID-TISSUE IN ATHYMIC NUDE-MICE

It has been suggested that ITL are of importance in the pathogenesis o f human autoimmune thyroid disease. Aim of our study was to investigat e function and morphology of xenotransplanted human thyroid tissue in nude mice following systemic application of lymphocyte preparations fr om patients with Graves' disease (GD) and non-toxic nodular goiter (NT G). ITL obtained from 13 patients with GD and peripheral blood lymphoc ytes (PBL) from 12 patients with NTG were injected into nude mice bear ing 8 weeks old xenografts of normal human thyroid tissue. ITL- and PB L-subsets were analyzed by flow cytometer (FACScan) before engraftment . Two days after injection the thyroid transplants were examined histo logically (HE) as well as immunohistologically by staining with: CD3, CD31, CD45R, HLA class II, ICAM-1, VCAM-1, IgG, IgM and Ki67. Flow cyt ometry showed a significant higher number of the lymphocyte-subsets CD 3, DR+ and CD4 in GD-ITL as compared to the subsets in NTG-ITL. After injection of GD-CD3+ human lymphocytes was found in the transplants. G D-lymphocytes stimulated thyroid tissue function significantly more pr onounced than NTG-lymphocytes (histomorphological evaluation). In addi tion, a significant increase of HLA-class II, ICAM-1-, VCAM-1-, CD45-e xpression and number of Ig presenting plasma cells were observed only after injection of GD-ITL. Our data demonstrate, for the first time in vivo (nude mouse model), that GD-lymphocytes of both peripheral and i ntrathyroidal origin selectively migrate into human thyroid transplant s (''homing''). They survive there for at least two days and induce si gnificant functional as well as histological changes, like expression of gene products and IgG synthesis. These results suggest an important role of ITL in the pathogenetic mechanisms and clinical course of GD.