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.

Under these conditions of infection, MCMV elicited more spontaneous IFN-␥ production from spleen, PECs, and liver NK cells at 2 d after infection than did the other viruses, as discussed earlier, presented in Fig. 4 A, and as shown in a control representative experiment for MCMV in Table I . We did not systematically analyze whether these other viruses would induce substantially higher levels of IFN-␥ from NK cells under conditions of different doses or times of infection, but it is noteworthy that none induced as high a proportion of NK cells producing IFN-␥ as MCMV under the tested conditions, which, as shown in Fig. 1 , stimulated strong NK cell responses. Nevertheless, all viruses did stimulate spontaneous IFN-␥ production from some of the NK cells. Of note is that we did not observe spontaneous IFN-␥ production by NK cells from mice treated with the type I IFN inducer and NK cell activator poly I:C (data not shown). It has been published previously that NK cells from MCMV-infected but not LCMV-infected mice produce IFN-␥, and this has been linked to differences in IL-12 production (35). Here we do see quantitative differences between the MCMVand LCMV-induced NK cells, but substantial numbers of LCMV-induced NK cells clearly synthesized IFN-␥.