Thymic epithelium and the induction of transplantation tolerance in nude mice.

Abstract

Immunological tolerance of self has been studied experimentally by the induction of unresponsiveness to antigens of the major histocompatibility complex (MHC) in neonatal mice. The specific unresponsiveness resulting from such neonatal tolerance induction is first demonstrable in the thymus, suggesting that neonatal tolerance is induced by some cellular component of the thymus, or at some prethymic stage. Recent transplantation studies suggest that thymic epithelium, derived by organ culturing fetal mouse thymus in the presence of deoxyguanosine, survives in an allogeneic host environment despite the continued expression of MHC donor antigens, but fails to induce allotolerance. We demonstrate here that embryonic thymus lobes organ cultured at 24 degrees C, a treatment that deletes the lymphohaematopoietic component of thymus leaving the epithelial matrix intact, when transplanted to intact histoincompatible recipients, similarly survive for a prolonged period and do not induce tolerance to donor MHC antigens. However, when such culture-derived thymic epithelium is allografted to athymic nude mice, host-derived lymphocytes from both the epithelial graft and recipient spleen are unresponsive to the MHC antigens of the epithelial donor. The results suggest that, when investigated in a system which precludes the possible involvement of extrinsic mature T cells, processed by the syngeneic host thymus, thymic epithelium may induce transplantation tolerance.