Concomitant killing in vitro of both gp120-coated CD4+ peripheral T lymphocytes and natural killer cells in the antibody-dependent cellular cytotoxicity (ADCC) system

NK cells play an important immunoregulatory role in first line defense mechanisms against infection. As disease progresses, HIV-1 infected patients show loss of NK cytotoxic function, down-modulation and/or loss of expression of both CD16 and CD56 surface Ags on NK cells and a gradual loss of both CD4+ T cells and NK cell numbers. A potential mechanism by which these manifestations may occur in vivo was investigated. We hypothesized that NK-mediated Ab-dependent cellular cytotoxicity (ADCC), using gp120-coated CD4+ peripheral T lymphocytes as targets and anti-HIV serum, will result in the concomitant killing of the CD4+ T lymphocyte targets and the NK lymphocytes. This hypothesis was examined in an in vitro model system. The findings demonstrate that gp120-coated peripheral T lymphocytes can serve as targets and are killed in ADCC. Further, the NK cells that recover from the ADCC reaction show a loss of cytotoxic function, acquire the CD16(dim/-) CD56(dim/-) phenotype and a significant fraction is killed by activation-induced cell death or apoptosis. These findings are reminiscent of the properties of circulating NK cells in HIV-infected patients. The implication of these findings in the pathogenesis of AIDS is discussed.