Characterization of CD56~-/CD16~+ natural killer (NK) cells: A highly dysfunctional NK subset expanded in HIV-infected viremic individuals

摘要

Natural killer (NK) cells are an important component of the innate immune response against viral infections. NK cell-mediated cyto-lytic activity is defective in HIV-infected individuals with high levels of viral replication. In the present study, we examined the pheno-typic and functional characteristics of an unusual CD56~-/CD16~+ (CD56~-) NK subset that is greatly expanded in HIV-viremic individuals. The higher level of expression of inhibitory NK receptors and the lower level of expression of natural cytotoxicity receptors observed in the CD56~- NK fraction compared with that of CD56~+ NK cells was associated with extremely poor in vitro cytotoxic function of this subset. In addition, the secretion of certain cyto-kines known to be important in initiating antiviral immune responses was markedly reduced in the CD56~-, as compared with the CD56~+ NK cell subset. These data suggest that the expansion of this highly dysfunctional CD56~- NK cell subset in HIV-viremic individuals largely accounts for the impaired function of the total NK cell population.