T cell tolerance in Moloney-murine leukemia virus (M-MuLV) carrier mice: Low cytotoxic T lymphocyte precursor frequency and absence of suppressor T cells in carrier mice with Moloney-murine sarcoma (M-MSV)-induced tumors

Mice neonatally injected with Moloney-murine leukemia virus (M-MuLV) become permanent virus carriers and, in contrast to normal mice, fail to reject Moloney-murine sarcoma virus (M-MSV)-induced tumors as adults (progressor mice). Failure of tumor rejection has been shown to correlate with lack of T cell responsiveness of lymphoid cells from carrier mice in terms of tumor-specific cytotoxic T lymphocyte (CTL) generation in vitro and with failure to transfer protection against tumor growth in T cell-deficient mice. Since, in addition, lymphoid cells of carrier mice failed to suppress CTL generation in vitro by M-MSV-immune spleen cells, it was concluded that neonatal M-MuLV injection resulted in a state of T cell tolerance. Recent reports have suggested that carrier mice injected with M-MSV (progressor mice) generate suppressor cells that mediate enhanced tumor growth and inhibit CTL generation in vitro. In the present report, we fail to confirm these findings by demonstrating that: a) Neither carrier nor progressor spleen cells suppress the tumor protective effect of M-MSV-immune cells in T-deficient mice. b) Progressor spleen cells fail to suppress M-MuLV-specific CTL generation by immune cells. c) Spleens of carrier mice contain 100-fold lower M-MuLV-specific CTL precursors than do spleens of normal mice, and spleens of progressor mice contain over 1000-fold lower CTL-precursor frequencies than do spleens of regressor mice. d) Spleen cells from progressor mice fail to inhibit the clonal response of small numbers of CTL precursors in micro mixed leukocyte tumor cell cultures. Thus, these results support the hypothesis that M-MSV tumor progression in carrier mice is due to reduction in virus-specific CTL precursor frequency and not to the generation of suppressor cells.