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.

One family of mouse NKR molecules is the Ly49 group, which now consists of a variety of C-type lectin molecules, designated A through W. The Ly49 gene family maps near the positive-triggering molecule NKR-P1 (defined by mAb NK1.1) in the area of chromosome 6, known as the NK cell complex (5, 6) . Of note is that genetic resistance and susceptibility to murine cytomegalovirus (MCMV) maps within this region at a locus designated Cmv-1 (7) . The evidence implicating NK cells in the control of MCMV infection is stronger than for any other infectious agent. Suckling mice are very sensitive to MCMV infection, but a level of resistance develops at about the third week of age, correlating not only with the develop-30 Control of MCMV by an NK Cell Subset ment of NK cell activity but also with the expression of Ly49 molecules on a high frequency of NK cells (8, 9) . Reconstitution of suckling mice with NK cells in adult splenocytes or with IL-2-activated, cultured lymphokineactivated NK cells confers resistance to infection (10, 11) . Depletion of NK cells with anti-NK cell Abs in normal, athymic nude, or severe combined immunodeficiency mice results in substantially elevated titers of MCMV early in infection (12) (13) (14) (15) (16) . Mice with genetic deficiencies in NK cell function are very sensitive to MCMV (17) . Together these experiments indicate that classically defined CD3 Ϫ NK cells, as opposed to NK/T cells, provide innate immunity to MCMV.