Class I MHC Antigens and the Control of Virus Infections by NK Cells

Due to their ability to lyse virus-infected cells before the release of mature virions, cytotoxic lymphocytes are among the most important host defense mechanisms against viral infections. The two major forms of cytotoxic lymphocytes are the natural killer (NK) cells and the cytotoxic T lymphocytes (CTL), which peak in response at early and late stages of infection, respectively. Mouse NK cells, defined here as CD3−, TCR−, NK1.1+, asialo GM1 + lymphocytes, are normally slowly dividing cells that lyse a limited range of “NKsensitive” targets, but the interferon (IFN)-α/β induced during virus infection augments their cytolytic potential, enabling them to lyse most types of targets, and, most likely in concordance with other growth factors, stimulates their proliferation (Welsh, 1986). NK cells accumulate at sites of virus infection and may represent up to 20% of the infiltrating leukocyte population by 3 days postinfection (McIntyre and Welsh, 1986; Natuk and Welsh, 1987). Concomitantly, clones of CTL precursors recognizing viral peptides displayed on class I major histocompatibility complex (MHC) antigens proliferate and differentiate in response to IL-2 and IFN-γ and become detectable at later (day 6–10) stages of infection (Welsh, 1986; Townsend and Bodmer, 1989). At this later time the NK cell response diminishes, due both to a decrease in the levels of virus, which stimulate the IFN-α/β response, and due to suppressive effects of transforming growth factor-β produced predominantly by activated macrophages (Su et al., 1991).