Production of migration inhibition factor by spleen cells of normal rats upon culture in vitro with tumor cells and cells expressing endogenous virus

Spleen cells from normal rats of W/Fu, Fischer, Sprague-Dawley, and BDIX strains produced migration inhibition factor (MIF) upon culture in vitro with puromycin-treated rat cell lines expressing leukemia viruses or endogenous C-type viruses. Brown Norway rats were almost invariably unreactive. The MIF reactivity of most normal rats did not appear to be due to environmental stimuli because germfree rats were also positive. There was no apparent age restriction for expression of MIF activity; spleen cells from 1-week-old rats produced detectable levels of MIF, and this reactivity was also found in the oldest tested rats, at 34 weeks of age. In addition to spleen cells, lymphoid cells from the blood, peritoneal cavity, and lymph nodes, but not thymus, also were able to produce MIF in response to tumor cells. When (C58NT)D tumor cells, which were routinely used as the stimulators of MIF production, were inoculated into W/Fu rats, the characteristics or extent of preexisting reactivity were not altered. However, spleen cells of most rats bearing progressively growing (C58NT)D tumors did not show a MIF response in vitro. MIF production by spleen cells was dependent upon the presence of macrophages. Spleen cells depleted of phagocytic and adherent cells were unable to produce MIF upon incubation by tumor cells; however, the MIF response could be restored by adding allogeneic or syngeneic macrophages to the depleted spleen cells. The helper role of macrophages in the generation of MIF by spleen cells did not appear to involve antigen presentation because direct contact between macrophages and the responder cells was not necessary, and soluble factor(s) released by macrophages could substitute for the macrophage helper function. The effector cells of MIF production were nonadherent, lacked detectable Fc receptors for IgG, and were resistant to lysis by anti-T cell serum plus complement. Because the MIF response was present in apparently normal rats, this appears to be an expression of natural immunity that may be analogous to natural killer cell activity.