Immunological tolerance in the mouse thymus cell population induced by the intravenous injection of deaggregated bovine gamma globulin was terminated by whole body irradiation. After irradiation, the weight of the thymus recovered biphasically, and the termination of tolerance occurred as early as in the first phase. Both Thv-I antigen expression and helper activity of the thymus cell population in irradiated mice recovered in parallel with the recovery of the thymus weight. Sensitivity of the regenerating thymus cells to the tolerogen was not different from that of the normal thymus cells. The first phase of thymus regeneration may be caused by the proliferation and differentiation of relatively radioresistant and tolerogen insensitive precursors residing in the thymus. Tolerogen and/or immunogen reactive thymus cells may originate from the precursor.Mouse thymic lymphocytes are known to originate from precursor cells in the bone marrow (11,19,27). The precursor cells proliferate and differentiate into thymic lymphocytes having unique functions and surface markers under the influence of the thymic environment (6,20,26). For investigating the characteristics of thymic lymphocyte precursors, thymus regeneration after irradiation has presented a good model for the maturation of thymic lymphocytes, since the regeneration seems to recapitulate, at least partly, the developmental process of thymic lymphocytes (5, 10,32).The tolerant state induced by deaggregated heterologous proteins persists for a long time in thymic lymphocyte and peripheral T cell populations (34). Although such long-term maintenance of tolerance may be attributable to slow turnover of T cells in the thymus and in the recirculating pool, recovery from tolerance is markedly retarded by thymectomy of the tolerant animal (8). This seems to indicate that lymphocytes formed in the thymus after the induction of tolerance are progeny of tolerogen-insensitive, or antigen-uncommitted, precursor cells.The present study was undertaken to investigate the relationship between the development and the antigen sensitivity of thymus cells. Thus, primary interest
