Lack of M-MuSV tumour regression associated with T lymphocyte tolerance

Abstract

Moloney murine leukaemia virus (M-MuLV) and Moloney murine sarcoma virus (M-MuSV) are competent and replication defective forms, respectively, of a type C retrovirus which is oncogenic in some inbred mouse strains¹. M-MuLV induces lymphomas, mostly of T lymphocyte origin, following injection into newborn animals. M-MuSV together with M-MuLV, its natural helper, and in the absence of an appropriate immune response can elicit the formation of an unusual sarcoma which may grow and kill. This sarcoma is unusual in that, at least initially, it is a polyclonal entity within which continual recruitment of previously uninvolved mesenchymal cells occurs². Resistance to the induction of tumours by M-MuSV is thought to depend on activation of appropriate T lymphocytes. The main evidence for this is the finding that animals numerically deficient in T lymphocytes are highly susceptible to sarcoma induction^3–5 and that normal mice and previously challenged animals can generate T lymphocytes specifically cytotoxic in vitro for tumour cells carrying viral antigens⁶. Animals injected with M-MuLV at birth are susceptible to M-MuSV challenge and incapable of generating cytotoxic T lymphocytes active against virus-infected cells in vitro^7,8. On the other hand, the M-MuLV neonatally injected animals immunized as adults against allogeneic leukaemic cells are fully competent in generating alloreactive cytotoxic T lymphocytes⁸. T-cell deficient mice can in addition be reconstituted in their capacity to resist challenge by M-MuSV by implantation of syngeneic thymus grafts or injection of normal T lymphocytes^4,5. The exact role of T lymphocytes in the control of the acute phase of the infection with M-MuSV is not certain but it probably involves a cytotoxic capacity of T cells comparable with that seen in vitro. The role of antibody in bringing about resistance is not clear, as passive immunization per se is relatively ineffective in preventing tumour growth in T-cell deficient mice⁵, as was transfer of specifically primed B cells (our unpublished data). We present here evidence that neither thymuses nor peripheral lymphocytes removed from mice injected with M-MuLV at birth are capable of reconstituting T-cell deficient mice in such a manner as to promote resistance to challenge with M-MuSV.