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Resistance to Tumor Growth Mediated by Listeria Monocytogenes: Collaborative and Suppressive Macrophage-Lymphocyte Interactions in Vitro¹

Department of Pathology, University of California San Diego, School of Medicine, La Jolla, California 92037

Abstract

Spleen (SC) and peritoneal cells (PC) from C57BL/6 mice immune to Listeria monocytogenes (LM) have a marked cytotoxic effect on the in vitro growth of B-16 melanoma. Cytotoxicity to B-16 is mediated by the interacting sensitized thymus-derived (T) lymphocytes and macrophages (Mø) or adherent cells. Separation of immune SC or PC into their adherent and nonadherent components, depletion of the adherent cells or elimination of the -bearing cells from an enriched T cell population all result in the abrogation of cytotoxicity, whereas, recombination of T cells and Mø re-establishes this effect. Three modes of Mø/T cell interactions occur: 1) LM immune peritoneal or splenic T cells interact or synergize with their respective adherent cells to become cytotoxic to B-16; 2) combination of peritoneal Mø and splenic T cells are noncollaborative and therefore noncytotoxic; 3) the cooperative effect of spleen T cells with Mø are suppressed or inhibited by addition of peritoneal Mø. Splenic Mø, however, are neither uncooperative nor inhibitory when interacting with peritoneal T cells. Normal adherent cells can substitute for immune cells in all the cell-cell interactions with similar end results. These results demonstrate that specifically sensitized T cells interact with Mø for expression of LM-induced nonspecific tumor cell destruction in vitro, however, such interactions may also be noncooperative or suppressive, thus resulting in tumor cell proliferation.

Footnotes

¹ This investigation was supported by the United States Public Health Service Grants CA 15240, CA 17299, and HL 14169.