In vitro production of immunosuppressive factors by murine sarcoma virus-transformed mouse fibroblasts.

Abstract
Murine sarcoma virus-transformed mouse fibroblast cells produce potent immunosuppressive factors (ISF) in vitro. The partially purified ISF inhibited thymocyte proliferation induced by concanavalin A or phytohemagglutinin plus lymphocyte activating factor (Interleukin 1), lipopolysaccharide-induced spleen cell proliferation, the in vitro splenic anti-sheep erythrocyte plaque forming cell response and the generation of alloantigen-specific cytotoxic T[thymus-derived] cells. The effect of ISF on thymocyte proliferation was not readily reversible and required only a 4 h exposure of the thymocytes to ISF to inhibit cell proliferation. Although ISF shares several biochemical properties with a murine sarcoma virus-transformed cell-derived sarcoma growth factor (e.g., acetic acid solubility and sensitivity to dithiothreitol), the 2 factors could be resolved by gel filtration on Bio-Gel P-60. Two peaks of ISF activity were found with apparent MW of 12,000 and 8000. The hypothesis that at least some of the ISF obtained from the serum of tumor-bearing hosts may be released by the tumor cells themselves is supported. In view of the potent in vitro activity of the murine sarcoma virus-transformed fibroblast-derived ISF, it is quite possible that ISF-like molecules may play a role in subverting in vivo tumor rejection processes involving the immune system.