CD56 negative NK cells: origin, function, and role in chronic viral disease

Natural killer (NK) cells serve as a first line of defense against acute viral infections. Immunogenetic association data suggest that NK cells also influence the course of chronic viral infections, such as infections with HIV-1 and hepatitis C virus (HCV). Chronic stages of these infections have a negative impact on NK cell function and promote the appearance of phenotypically and functionally abnormal NK cells. In this paper, we summarize available data on CD56neg NK cells, an aberrant NK cell subset found in small numbers in healthy individuals and at elevated levels in individuals chronically infected with HIV-1 and HCV. We discuss current knowledge of CD56neg NK cells, with a particular emphasis on their accumulation during chronic infection and the possible consequences of this for the host.