Immunosuppression and malignant lymphomas in graft-versus-host reactions.

The immune responses of mice undergoing the graft- versus -host reaction were tested with a battery of four antigens. Three donor-host combinations were selected on the basis of their susceptibility to the development of malignant lymphomas. The results were highly variable. In general, antigens eliciting responses independent of thymus-derived (T) cells (lipopolysaccharide) or bone marrow-derived cells (skin allograft rejection) were normal, whereas antigens eliciting cooperative responses between T- and bone marrow-derived-cells (sheep red blood cells and dinitrophenyl-keyhole limpet hemocyanin) were depressed. Augmentation of primary immune responses by the graft- versus -host reaction was found in four different experiments. Evidence for an environmental immunosuppressant could not be found. Deliberate immunosuppression of otherwise normal mice with anti-mouse thymocyte serum failed to cause the appearance of tumors. Those mice with the lowest incidence of lymphomas developed severe depression of certain of their immune responses. Under the experimental conditions that we studied, it appears that the graft- versus -host reaction can: ( a ) block cooperation between T- and bone marrow-derived cells; ( b ) augment certain immune responses, perhaps by means of stimulants released from T-cells; and ( c ) provoke the development of lymphomas in a setting devoid of significant immunosuppression.