Natural killer NK cells

In contrast to nonproliferating T and B lymphocytes, NK cells have large, active cytoplasms capable of supporting virus growth. Little is known about the frequency or significance of virus infections of NK cells in vivo, but cytomegalovirus (CMV), measles and influenza viruses infect human NK cells in vitro. These infections are not lytic, and influenza virus does not inhibit NK cell-mediated cytotoxicity; in contrast, both CMV and measles virus inhibit the ability of NK cells to mediate natural cytotoxicity but do not impair their ability to mediate antibody-

dependent cellular cytotoxicity (ADCC). The reason for this selective inhibition in lytic function is not known, but it is of interest that some strains of HIV can infect NK cells and that NK cells isolated from patients infected with HIV similarly display a selective defect in natural cytotoxicity but not ADCC. Also during HIV infection there is a sclcctive loss of CD8+ NK cells; it has been suggested that HIV infection of CD8+ NK cells leads to tumor necrosis factor a (TNFa) production, which activates HIV synthesis, resulting in lysis of the cell, whereas the predominant cytokine made in CD8~ NK cells is interferon a (IFNa), which inhibits viral synthesis and protects the cell. The cytotoxic mechanism of NK cells can be triggered directly by treatment with glycoproteins isolated from a variety of viruses, including mumps, measles, influenza, Sendai, and lymphocytic choriomeningitis viruses, and this may provide a means by which NK cells can selectively lyse virus-infected targets.

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