Elevated natural killer cell responses in mice infected with recombinant vaccinia virus encoding murine IL-2

The role of cytotoxic T cells and NK cells in the recovery of immunodeficient, athymic, nude mice infected with a recombinant vaccinia virus (VV) encoding murine IL-2 was investigated. Kinetic studies with the IL-2-encoding recombinant (VV-HA-IL2) and control (VV-HA-TK) viruses excluded a role for cytotoxic T cells but suggested the possible involvement of NK cells. In athymic nude mice given VV-HA-IL2, NK activity was at least threefold higher than mice infected with VV-HA-TK and this activity persisted for at least 6 days after infection. The effectors mediating the NK-like activity were asialo-GM1+ (as-GM1+), Thy1.2+/-, CD4- and CD8-, the phenotype of conventional NK cells. Elevated NK activity coincided with the rapid clearance of VV-HA-IL2 from ovaries of infected normal CBA/H mice but not from ovaries of CBA beige mice which had no detectable NK activity in spleens or ovaries. The expression of IL-2 in recombinant VV infection probably induces a cascade of immunologic effects of which elevated NK activity is one. We speculate that the chemoattractant and NK activity augmenting effects of IL-2 may contribute to recovery from VV-infection.