Murine Cytomegalovirus Is Regulated by a Discrete Subset of Natural Killer Cells Reactive with Monoclonal Antibody to Ly49h

Daniels, Keith A.; Devora, Gene; Lai, Wayne C.; O'Donnell, Carey L.; Bennett, Michael; Welsh, Raymond M.

Selective Depletion of NK Cell Subsets In Vivo. To address the role of Ly49 subsets in regulating MCMV infection in vivo, mice were inoculated with mAb to Ly49 molecules in order to deplete various NK cell subsets. Our previous studies with in vivo-depleting doses of mAb to Ly49A, D, C/I, and G2 indicated that no one or two of them had any effect on MCMV synthesis, and combinations of three of them had little effect (22) . As shown in Fig. 4 , a substantial proportion of the spleen NK cells initially react with mAb 1F8 before infection, but this is no higher than those expressing Ly49G2 or combinations of two of the other Abs. Of note is that a substantial number of liver and PEC NK cells do not react with 1F8 before infection. Treatment of four naive mice in two experiments with 200 g of mAb 1F8 resulted in ‫%05ف‬ reduction in spleen NK cell-mediated cytotoxicity against YAC-1 activity when measured 1 d later. Immunofluorescent studies showed that mAb 1F8 treatment caused only a marginal (Ͻ30%) reduction in total spleen NK cell number 1 d after treatment, even though 1F8 ϩ NK cells could not be found (data not shown). NK cells usually rapidly compensate for the lack of an NK cell subset. Mice treated with mAb 1F8 and then infected with LCMV had nearly identical levels of NK cell cytotoxicity against YAC-1 cells as untreated mice 3 d after LCMV infection, and mice treated with mAb to 1F8 and challenged with the IFN-inducer poly I:C had levels of NK cell activity similar to poly I:C-injected control mice at 2 d after treatment (data not shown).