Role of natural killer cells in resistance against Friend retrovirus-induced leukemia

We have previously shown that immunization with a synthetic peptide that co ntains a single CD4(+) T-cell epitope protects mice against immunosuppressi ve Friend retrovirus infection, Cells producing infectious Friend virus wer e rapidly eliminated from the spleens of mice that had been immunized with the single-epitope peptide. However, actual effector mechanisms induced thr ough T-helper-cell responses after Friend virus inoculation were unknown. W hen cytotoxic effector cells detected in the early phase of Friend retrovir us infection were separated based on their expression of cell surface marke rs, those lacking CD4 and CD8 but expressing natural killer cell markers we re found to constitute the majority of effector cells that lysed Friend vir us-induced leukemia cells. Depletion of natural killer cells by injecting a nti-asialo-ganglio-N-tetraosylceramide antibody did not affect the number o f CD4(+) or CD8(+) T cells in the spleen, virus antigen-specific proliferat ive responses of CD4(+) T cells, or cytotoxic activity against Friend virus -induced leukemia cells exerted by CD8(+) effector cells. However, the same treatment markedly reduced the killing activity of CD4(-)CD8(-) effector c ells and completely abolished the effect of peptide immunization, Although the above enhancement of natural killer cell activity in the early stage of Friend virus infection was also observed in mice given no peptide, these r esults have demonstrated the importance and requirement of natural killer c ells in vaccine-induced resistance against the retroviral infection.