Muramyl Dipeptide Induced Augmentation of the Proliferative Response of Thymocytes to Phytohemagglutinin

N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) augmented the proliferative response of thymocytes to phytohemagglutinin (PHA). The augmenting effect of MDP disappeared by passage of glass-nonadherent thymocytes through Sephadex G-10 (G-10) column or by removal of low density cells by the Ficoll-Conray gradient centrifugation. The diminished augmenting effects of MDP on the proliferative response of glass-nonadherent-G-10 nonadherent thymocytes was restored by the addition of the G-10 adherent cells. When G-10 adherent cell fraction was extensively depleted of macrophages by glass adherence and EA-rosetting, it was found that neither the macrophage-depleted G-10 adherent cell fraction nor the macrophage fraction supported by itself the proliferative response of G-10 nonadherent thymocytes. However, addition of macrophage fraction together with the macrophage-depleted G-10 adherent cells did support the proliferation of G-10 nonadherent thymocytes. It was further shown that peritoneal exudate macrophages could be substituted for thymic macrophage fraction. These results suggested that both the G-10 adherent-glass nonadherent cells and macrophages were essential for the MDP-induced augmentation of the proliferative response of thymocytes to PHA and these cells exerted different accessory roles in this response.