Protection of mice from lethal influenza by defective interfering virus: T cell responses.
The immune-mediated lethal influenza in C3H/He-mg (H-2k) 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.
Department of Biological Sciences, University of Warwick, Coventry, U.K.
L
L
McLain
D J
DJ
Morgan
N J
NJ
Dimmock
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003673:Defective Viruses / Q000276:immunology*; D000939:Epitopes; D005260:Female; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000939:Epitopes