Mice infected with a wild mouse-derived ecotropic murine leukemia virus (Cas-Br-M) develop a wide spectrum of hematopoietic tumors. To determine if these tumors were caused by the parental virus or newly-induced recombinant viruses with lineage specificity, mice were infected with extracts of primary tumors induced by Cas-Br-M. Two lineage-specific viruses were recovered. One, Cas NS-6 is a unique MCF virus that induces T cell lymphomas with short latency without the requirement for ecotropic virus. The second, Cas NS-1, is a replication defective virus that transforms fibroblasts in vitro and induces predominantly pre-B cell lymphomas in vivo. Additional studies of tumors induced by these extracts showed that interleukin 3-dependent cell lines with myeloid characteristics were obtained from myelogenous and erythroleukemias but rarely from lymphoid neoplasms. Resistance to ectromelia virus infection is determined by cytotoxic T lymphocyte responses. Studies of mice depleted in vivo of L3T4+ cells demonstrated that they produce normal responses to ectromelia and survive the infection. These results provide the first in vivo evidence for a helper cell-independent pathway for generation of cytotoxic T lymphocytes.
