In vivo acute depletion of CD8+ T cells before murine cytomegalovirus infection upregulated innate antiviral activity of natural killer cells

In this study, we investigated the effect of depletion of CD8⁺ T cells on the activity of natural killer (NK) cells at an early phase of murine cytomegalovirus (MCMV) infection. For CD8⁺ T cell depletion, mice were intraperitoneally treated with anti-CD8 mAb, purified from 2.43 hybridoma, for 2 consecutive days before or after infection. Three days after infection, we found that an acute depletion of CD8⁺ T cells before infection caused a significant decrease in the viral load in liver and spleen. This effect coincided with an increase in numbers of CD3⁻ NK1.1⁺ cells in spleen and their expression of the early activation molecule CD69. Although cytolytic activity of NK cells increased on day 3 of infection in CD8-depleted mice, the level of IFN-γ decreased in serum and supernatant of cultured spleen cells. In contrast to the effect of acute depletion of CD8⁺ T cells before infection, the depletion after infection had no effect on the viral load or number and cytolytic function of NK cells. Lack of effects of CD8⁺ T cell depletion on the viral load and NK cytolytic activity is also observed in CD8⁺ knockout mice. In conclusion, the results suggest that an acute depletion of CD8⁺ T cells before MCMV infection effectively upregulated the antiviral activity of NK cells. This effect appears to be mediated through an increase in numbers, activation and cytolytic activity of NK cells.