Augmenting effect of exogenous macrophages on the rat graft-versus-host reaction in F1 hybrids depleted of macrophages.

The crucial role of macrophages in the generation of the rat graft-versus-host reaction (GVHR) was investigated in normal and macrophage-depleted F1 hybrid rats. The addition of exogenous macrophages, colloidal carbon, or lipopolysaccharide (LPS) resulted in a great augmentation of GVH reactivity of parental lymph node cells in normal F1 hybrid rats. Uptake of foreign materials by F1 macrophages exerts a biphasic action on the GVHR, activating or blocking the biological activity. This depends on the time of injection of foreign materials. To define the extent of macrophage dependence in the GVHR, the additive effect of exogenous macrophages on the reaction was investigated in F1 hybrid rats depleted of effective macrophages and lymphocytes, which had received preliminary host irradiation and colloidal carbon injection. In F1 hybrids depleted of macrophages and given injections of parental lymph node cells depleted of macrophages, the addition of exogenous F1 macrophages resulted in a much higher reaction than did lymphocytes alone. The data suggest that macrophage-induced augmentation of the reaction may be a reflection of the regulatory function of macrophages in the cellular interactions between parental GVH-reactive lymphocytes and alloantigen-bearing host cells in vivo.