Reversal of Antilymphocytic Serum-Induced Immunosuppression By Macrophage Administration 1

Abstract

The key role of the macrophage as the afferent component of the immune reflex arc is well documented (6–8, 10, 11, 19, 22, 31). Furthermore, Frei et al. (9) demonstrated that phagocytosis is an essential step in the development of the primary immune response while others have shown that the transplantation of macrophages into newborn mice (1) and rabbits (19) will promote the early development of immunocompetence. In view of these findings, it would be expected that the administration of chemotherapeutic agents which alter the normal phagocytic function of the reticuloendothelial system (RES) would induce a corresponding alteration in the immune response. Indeed, Wooles and Di Luzio (31) initially demonstrated that RES depression was associated with a decreased immune response while RES stimulation resulted in an increased antibody titer.

Previous studies from this laboratory (25) have shown that a single injection of antilymphocytic serum (ALS) impairs phagocytic activity of the reticuloendothelial system (RES), as reflected by a depressed intravascular clearance rate of gelatinized RE test lipid emulsion. The ALS-induced depression in phagocytosis was associated with a selective decrease in Kupffer cell phagocytosis. In vitro studies which employed both serum and liver slices derived from either normal or ALS-treated animals also indicated the ability of ALS to induce phagocytic impairment. These in vitro studies (25) suggested that the depression of RES activity by ALS could be attributed to an exclusive defect in the cellular compartment of the RES since no alteration in circulating phagocytic-promoting activity was found in ALS-treated animals. Furthermore, a direct injurious effect of ALS on Kupffer cells was demonstrated, not only by ALS-induced impairment of Kupffer cell phagocytic activity, but also by the cytotoxic action of ALS on these macrophages (25).