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.

Infections. The NK cell response against MCMV ( Fig. 1 A) , MHV ( Fig. 1 A) , VV ( Fig. 1 B) , and a disseminating strain of LCMV (clone 13) (Fig. 1 B) was examined initially during the first 3 d of infection of C57BL/6 mice. Here spleen, peritoneal cavity, and liver NK cells, defined as NK1.1 ϩ CD3 Ϫ , were quantified, and their total numbers and percentages within lymphocyte-gated populations were enumerated, as shown in the vertical bars in Fig. 1 . Each virus infection initially caused a slight transient decrease in NK cell number and percent in the spleen, but each virus induced a substantial increase in NK cell number and percent in the peritoneal cavity, which was the site of viral inoculation. This increase in NK cells in the peritoneal exudate cells (PECs) with all of these viruses had been reported by us in the 1980s, when large granular lymphocyte morphology and Ab to asialo GM1 was used to define NK cells (29, 30) . NK 1.1 is a more specific NK cell marker, particularly when used on lymphocyte-gated cells that fail to stain with anti-CD3. It is now known that there are significant populations of "NK/ T" cells that costain with anti-NK1.1 and anti-CD3, and it is important to make those distinctions. In addition, we have found that VV induces a strong ␥␦ T cell response and that ‫ف‬ 1/3 of those ␥␦ T cells stain with anti-NK1.1 (31) . Each virus also stimulated an increase in the total number and percentage of NK cells in the liver, a result also previously noted by us using less definitive techniques (28) . These increases in NK cell numbers and percentages are very reproducible findings, though the degree and kinetics of the responses vary somewhat with virus dose. We have previously shown that NK cells migrate into areas of virus infection and undergo division in those areas (28) (29) (30) .