Vaccination with DNA encoding internal proteins of influenza virus does not require CD8(+) cytotoxic T lymphocytes: either CD4(+) or CD8(+) T cells can promote survival and recovery after challenge

DNA vaccination offers the advantages of viral gene expression within host cells without the risks of infectious virus. Like viral vaccines, DNA vacci nes encoding internal influenza virus proteins can induce immunity to conse rved epitopes and so may defend the host against a broad range of viral var iants, CD8(+) cytotoxic T lymphocytes (CTL) have been described as essentia l effecters in protection by influenza nucleoprotein (NP), although a lesse r role of CD4(+) cells has been reported. We immunized mice with plasmids e ncoding influenza virus NP and matrix (M). NP + M DNA allowed B6 mice to su rvive otherwise lethal challenge infection, but did not protect BG-beta(2)m (-/-) mice defective in CD8(+) CTL. However, this does not prove CTL are re quired, because beta(2)m(-/-) mice have multiple immune abnormalities. We u sed acute T cell depletion in vivo to identify effecters critical for defen se against challenge infection. Since lung lymphocytes are relevant to viru s clearance, surface phenotypes and cytolytic activity of lung lymphocytes were analyzed in depleted animals, along with lethal challenge studies. Dep letion of either CD4(+) or CD8(+) T cells in NP + M DNA-immunized BALB/c mi ce during the challenge period did not significantly decrease survival, whi le simultaneous depletion of CD4+ and CD8(+) cells or depletion of all CD90 (+) cells completely abrogated survival. We conclude that T cell immunity i nduced by NP + M DNA vaccination is responsible for immune defense, but CD8 (+) T cells are not essential in the active response to this vaccination. E ither CD4(+) or CD8(+) T cells can promote survival and recovery in the abs ence of the other subset.