Antigen activation of DNA synthesis in immune thymus-derived lymphocytes of guinea pigs requires the cooperation of macrophages and lymphocytes. We have investigated the role of histocompatibility determinants in this macrophage-lymphocyte interaction using cells from inbred strain 2 and 13 guinea pigs. The data demonstrate that efficient presentation of macrophage-associated antigen to the lymphocyte requires identity between macrophage and lymphocyte at some portion of the major histocompatibility complex. The failure of allogeneic macrophages to effectively initiate immune lymphocyte proliferation was not the result of the presence of an inhibitor of blastogenesis released in mixtures of allogeneic cells, peculiarities of the antigen or lymphoid cells employed, nor differing kinetics of activation by allogeneic macrophages. In addition, data were presented that demonstrated that alloantisera inhibit lymphocyte DNA synthesis by functional interference with macrophage-lymphocyte interaction.

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