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.

We questioned whether commercially available Abs to Ly49 molecules (A, C/I, D, G2) could detect qualitative differences in NK cell responses between organs and between viruses. These experiments showed a great deal of animal-to-animal variability, but some conclusions could be drawn. The first conclusion is that only a low percentage of resident NK cells in the liver before infection expressed these Ly49 antigens, with the exception of Ly49 C/I, which was lower but in the range of spleen and PEC percentages. A much higher frequency of the infiltrating NK cell population in the liver after virus infection expressed other Ly49 markers, in particular Ly49 D and G2, at frequencies more in line with other compartments. A second major conclusion is that within a mouse the relative frequencies of NK cells coexpressing Ly49 molecules change in relation to each other in different organs and at different times after infection. This indicates that these NK cell subsets are responding to signals induced by the viral infections differently, though it is less clear how different one virus was from the other at inducing these changes in NK cell distribution. In this experiment it appeared that all four viruses induced drops in Ly49C percentages in the spleen and rises in the PECs. Ly49G2 percentages rose in every organ with every infection. These observations were previously noted by us in more extensive analyses with MCMV (22) . A consistent result seen by us in three experiments was that the ratio of Ly49G2 ϩ to Ly49C/I ϩ liver NK cells at 3 d after infection was high (often Ͼ 2:1) after infection with MCMV, LCMV, or MHV, but the frequencies of Ly49G2 ϩ and Ly49C/I ϩ liver NK cells were about equal after VV infection ( Fig. 1 , and data not shown). These subtle differences suggest some selectivity in the NK cell responses to different viruses.