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Protection of mice from lethal influenza by defective interfering virus: T cell responses

Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, U.K.

The immune-mediated lethal influenza in C₃H/He-mg (H-2^k) 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 in vivo 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.

Received 3 September 1991; accepted 1 November 1991.

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