THE EFFECT OF CYTOTOXIC AGENTS ON THE PASSIVE TRANSFER OF CELL-MEDIATED IMMUNITY

A system involving the passive transfer of committed lymphoid cells from Listeria-immune donors has been used to study the phases of the immune response which are sensitive to the immunosuppressive action of various cytotoxic agents. The agents investigated included cyclophosphamide, vinblastine, methotrexate, azathioprine, and X-irradiation. Complete suppression of passive immunization was obtained by the administration of cyclophosphamide or vinblastine to recipients at the time of cell transfer or by prior X-irradiation of recipients a day before cell transfer. Methotrexate was only partially suppressive, whereas azathioprine had no effect at all. The donor cell responsible for the transfer of immunity to recipients was shown to be a resting cell which is sensitive to the action of cyclophosphamide but not to vinblastine. The results of this investigation suggest that the donor cells undergo multiplication in the tissues of the recipient, presumably in response to specific stimulation by Listeria antigens. This in turn results in the activation of host macrophages. The immunosuppressive action of cyclophosphamide, vinblastine, and irradiation in the cell-transfer system has been discussed in relation to a direct cytotoxic action on the immune lymphoid cells of the donor and specific interference with their proliferation in the recipient, as well as impairment of macrophage production on the part of the recipient itself.