Inhibition of In Vitro Growth of Lymphoma Cells by Macrophages From Tumor-Bearing Mice

Abstract

Spleen cells from C57BL/6 mice bearing primary tumors induced by the Moloney strain of murine sarcoma virus (MuSV) strongly inhibited the uptake of tritiated thymidine (3H-TDR) by RBL-5 lymphoma cells in a 48-hour growth-inhibition assay (GIA). This activity was first detected 7 days after MuSV was injected; it peaked at 14 days, and was usually no longer detectable after 18-21 days. It could be detected at effector cell/target cell ratios between 20:1 and 5:1, at which normal spleen cells had a growth-promoting effect. The effector cells in the GIA were not T cells, and various depletion experiments suggested that they were macrophages. Macrophages of a purity of over 95% were obtained in the glass-adherent fraction of thioglycollate-induced peritoneal exudate cells (PEC). PEC were growth inhibitory when obtained from either normal or MuSV tumor-bearing mice. However, at effector cell/target ratios of 2.5:1, only PEC from MuSV tumor-bearing mice had an effect; PEC from normal mice were inactive. Activity of spleen cells in the GIA appeared distinct from T-cell-dependent specific cytotoxicity, which was not affected by removal of macrophages. Activity in the GIA was nonspecific, and target cells which do not cross-react with RBL-5 cells were equally inhibited. Furthermore, spleen cells from mice bearing primary tumors induced by 3-methylcholanthrene were also fully active against RBL-5 cells. Supernatants from spleen cell cultures obtained from mice 14 days post injection with MuSV also inhibited the incorporation of 3H-TDR by RBL-5 cells in vitro. However, this effect seemed to be an artifact, since the tumor cells proliferated equally well in the presence or absence of the supernatants. In contrast, the direct effect of spleen cells from MuSV tumor-bearing mice was reflected both by an inhibition of cell proliferation and by inhibition of 3H-TDR incorporation.