Requirement of Histocompatible Macrophages for the Induction of a Secondary Cytotoxic Response to Syngeneic Tumor Cells in vitro

Abstract

Abstract The role of macrophages in the induction of secondary cytotoxic responses to syngeneic tumors was evaluated. When spleen cells from MSV-immune mice were extensively depleted of macrophages, they failed to mount an in vitro secondary cytotoxic response to syngeneic tumors. The response could be reconstituted by the addition of nonimmune macrophages, with syngeneic macrophages being much more efficient than allogeneic macrophages. The relative inefficiency of the allogeneic macrophages to restore the response was shown not to be due to: 1) induction of suppression by allogeneic cells, since in mixing experiments they did not inhibit the response; 2) differences in the kinetics of the response when allogeneic macrophages were employed; 3) requirements for different concentrations of syngeneic or allogeneic macrophages for this accessory function. Neither heat-killed nor frozen and thawed macrophages were capable of restoring the response. However, macrophages could still act as accessory cells if DNA synthesis was prevented. Furthermore, identity between macrophages and T lymphocytes at the I-A subregion of the MHC appeared to be necessary but perhaps not sufficient for an optimal response, and at this time it is not clear whether compatibility at other non-H-2 loci may also be required. The results of the present study suggest that macrophages serve an accessory function in the generation of a secondary cytotoxic response to tumor-associated antigens even when intact tumor cells are used as the stimulators.