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.

Ly49 Expression on and Fate of NK/T Cells during the Host Response to Viruses. There recently has been considerable interest in the potential role of T cells expressing NKRs in controlling infections and modulating host responses (33, (37) (38) (39) . Any experiments done using Abs to NKRs in vivo must be carefully interpreted due to the possibility of reactions with NK/T cells rather than "true" NK cells, which lack CD3 and T cell receptor expression. In the aforementioned experiments, where we examined NK1.1 ϩ CD3 Ϫ C57BL/6 mice were treated with mAb in HBSS or HBSS control, infected with virus, and examined for PFUs in spleen or liver 3 or 4 d later. PFUs represent either the titers per whole organ or per half organ, as in some experiments the spleens were cut in half in order to do analyses on the leukocytes. Each experiment had a n ϭ 4 or 5 per group, except for Exp. 5, which used T cell KO mice and n ϭ 3. The NK-resistant Armstrong strain of LCMV, which replicates poorly in liver, was used in these experiments, and for that reason liver titers were not assessed. The dosage of mAb was 200 g of mAb 1F8 in each experiment except for experiments 4, where 50 g was used and 5, where 25 g was used. mAb 5E6 was used at a concentration of 200 g. mAb to NK1.1 was used at dose previously determined to deplete NK cell but not CTL activity. Results presented are geometric mean titers, that is the arithmetic averages of the log values. The limits of detection were 1 log 10 PFUs in the spleen and 2 log 10 PFUs in the liver; these minimum detection values were entered into the calculations when no virus was found, and the ( Ͻ) designation means that at least one mouse had undetectable viral titers. Exp., experiment.