The immune-mediated lethal influenza in CH/He-mg (H-2) mice infected with A/WSN influenza virus (H1N1) was investigated. A primary class I major histocompatibility complex-restricted, CD8 cytotoxic T lymphocyte (CTL) response was found in the lungs with a peak activity at 5 days post-infection. Monoclonal antibody depletion showed that a lethal CD8 cell response as well as a lethal CD4 response was generated during infection. Mice survived infection only if both CD8 and CD4 cells were depleted. Mice infected with the same dose of virus, but treated with defective interfering (DI) A/WSN virus develop only a transient sub-lethal respiratory disease even though multiplication of virus in the lungs is undiminished, and we have shown here that this correlates with a reduction in the local CTL response. The mechanism by which DI virus beneficially modulates the immune response is discussed; it is proposed that there is classical, but cell type-specific DI virus interference in lymphocytes but not in the cells of the lung in which virus multiplies productively.


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