Role and specificity of T-cell subsets in spontaneous recovery from Friend virus-induced leukemia in mice

Spontaneous recovery from Friend virus complex-induced leukemic splenomegaly in H-2Db/b mice correlated with the appearance of Friend virus complex-specific cytotoxic T lymphocytes (CTL) detectable directly in spleen cell populations. By testing CTL on target cells containing expression vectors encoding individual retroviral structural proteins, the main viral protein recognized was shown to be the Friend murine leukemia helper virus envelope glycoprotein. In vivo depletion of CD8-positive T cells drastically reduced the incidence of recovery, providing direct evidence for the role of CD8-positive CTL in the spontaneous recovery process. In vivo depletion of CD4-positive cells had little effect on the early stages of recovery but did cause a marked reduction in the final incidence of recovery at 60 to 90 days. Thus, CD8-positive cells were required for the initiation of the recovery process, whereas CD4-positive cells appeared to be required for maintenance of the recovered status. Retroviruses are known to induce both neoplastic and nonneoplastic diseases in many species of animals and in humans (57). Protective immunity often can be generated by vaccination with killed virus or viral proteins prior to inoc-ulation of infectious retrovirus (18, 23, 25, 31, 44); however