The long-term objective of this project is to examine host/virus interactions that affect the immune response to murine leukemia virus (MuLV)-induced tumor transplantation antigens and, thus, influence resistance to MuLV-induced leukemogenesis. Previous studies have demonstrated that mice inoculated at birth with Gross leukemia virus (GV) are not capable of rejecting syngeneic GV-induced tumor cells or of mounting a T-cell response against these tumor cells, whereas both these events occur in normal mice. This specific nonresponsiveness to syngeneic tumor cells appears to occur, at least in part, as the consequence of the expression of virus antigena in radioresistant thymic stromal cells.
The specific aim of these studies is to determine if this specific nonresponsiveness is the result of the clonal elimination of virus-reactive T cells or the generation of suppressor cells. These studies will be done by two methods: (1) observing the effects on tumor rejection of dual thymus grafts, one from a neonatally infected donor, the other from a normal donor, and (2) examination of the possible immunosuppressive effects in adoptive transfer experiments of spleen cells from chimeras grafted with thymuses from neonatally infected mice on spleen cells from mice immunized with syngeneic tumor cells. Similar studies will be used to examine the effect of spontaneous neonatal expression of endogenous MuLV in AKR and H-2 congenic AKR-H-2?b? mice that develop a high incidence of spontaneous leukemia and, like adult mice inoculated with exogenous virus, fail to reject syngeneic tumor cells. In addition, our studies described should demonstrate for the first time a direct cause and effect relationship between the specific nonresponsiveness to virus-induced tumor transplantation antigens caused by the neonatal expression of MuLV and the development of leukemia. (SR)
