The contrasting effects of cyclophosphamide and radiation on the immune responses of the mouse.

The immunosuppressant cyclophosphamide easily induces specific immunological tolerance in CBA mice, but is unable to produce an immunological defect in adult thymectomized animals. In contrast, lethal (and sublethal) irradiation does not induce tolerance but readily brings out the deficit of thymectomy. Furthermore, bone marrow cells which protect lethally irradiated animals do not prevent drug deaths. This sharp dichotomy indicates that the drug and radiation influence the lymphoid system by different mechanisms. It seems likely from the work of others that cyclophosphamide action is markedly dependent on rapid cell proliferation, while radiation is not. From this it follows that the cell which must be depleted to expose the immune defect of the thymectomized animal is a nonproliferating lymphoid element with the slow mitotic rate of the marrow stem cell.