A study of the action of immunosuppressive factors from tumour cells on lymphocytes and macrophages in vitro and on the graft-versus-host reaction in mice.

The effect of immunosuppressive factors from P815, B16, and EL-4 mouse tumour cells on the permeability of the lymphocyte membrane to RNAase (the 'membrane-toxic effect'), on the generation of tumour necrosis factor (TNF) by mouse peritoneal macrophages, and on the survival rate of mice undergoing a graft-versus-host reaction was investigated. The immunosuppressive factors were found to have a membrane-toxic effect on mouse lymphocytes. Moreover, in the presence of pancreatic RNAase there was a dose-dependent increase in the inhibitory effect of the immunosuppressive factors on concanavalin-A-induced spleen cell proliferation. The immunosuppressive factors reduced the production of muramyl-dipeptide-induced TNF by mouse peritoneal macrophages. When immunosuppressive factors from P815 cells were administered to F1 hybrid mice (CBA x C57B1/6), there was a marked decrease in the intensity of the graft-versus-host reaction induced by injection of C57B1/6 parent mouse spleen cells to the F1 hybrids, and the life span of these mice was increased. It is suggested that the membrane-toxic effect may be one mechanism by which cells in the immune system are inhibited by immunosuppressive factors from tumour cells.