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.

NK/T cells were also monitored for their abilities to spontaneously synthesize IFN-␥ at 2 d after infection with MCMV. These NK1.1 ϩ CD3 ϩ cells accounted for Ͻ5% of the IFN-␥-producing NK1.1 ϩ cells in the spleen, PECs, or liver 2 d after MCMV infection; prototypical NK1.1 ϩ CD3 Ϫ true NK cells accounted for Ͼ95% of the IFN-␥ production within the NK1.1 ϩ population, and most of the IFN-␥-producing cells within the entire leukocyte population at 2 d after infection were NK cells, e.g., at 2 d after infection, 90% of the total IFN-␥-producing peritoneal lymphocytes were NK1.1 ϩ CD3 Ϫ NK cells. Similar dramatic enrichments in IFN-␥ production by the true NK cell population were also noted in LCMV, VV, and MHV infections. Therefore, we conclude that prototypical NK cells are the major IFN-␥-producing cells early in infection and that they are mediating the effects seem with the 1F8 mAb. The experiment showing enhanced MCMV synthesis in mAb 1F8-treated T cell KO mice (Table II) is consistent with this conclusion.