|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 2000 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1999 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1998 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Reconstitution of T cell functions in athymic BALB/c nude mice was investigated after transplantation of embryonic thymus grafts under the renal capsule (TG nude mice). Thymi were obtained from mice, rats, rabbits, hamsters, guinea pigs, swine and cows. All of the grafted thymi grew and formed proper thymic structure with host CD90 positive cells. The TCRβ expression pattern of the lymphocytes in the grafted thymi was quite similar to that of normal mouse thymocytes. Sufficient CD4 positive populations were observed in the peripheral lymphoid organs of all groups of TG nude mice. Plaque-forming cell assay revealed that the TG nude mice had acquired considerable helper T cell functions. Skin grafts from syngeneic mice and thymic donor rat strains were accepted, whereas those from allogeneic mice and the rats of other strains were vigorously rejected. Histological and serological studies, however, showed multiple organ-licalized inflammatory diseases in TG nude mice of all xenogeneic thymus groups, but not with syngeneic or allogeneic thymi. The organs affected were thyroid, the lacrimal, submandibular and sublingual glandsm, the eyes, stomach and ovaries. The incidence of lesions was variable depending on the species of origin of the grafted thymus. Development of autoimmune diseases in TG nude mice was prevented by a single injection of splenic CD4 positive cells from normal BALB/c mice. These results together suggested that the microenvironment of grafted thymi, even if xenogeneic, is able to educate host T cell precursors. However, this reconstitution of function does not always induce tolerance to certain autoantigens, resulting in development of multiple autoimmune lesions.