CONCOMITANT KILLING IN-VITRO OF BOTH GP120-COATED CD4(-LYMPHOCYTES AND NATURAL-KILLER-CELLS IN THE ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY(ADCC) SYSTEM() PERIPHERAL T)

NK cells play an important immunoregulatory role in first line defense mechanisms against infection, As disease progresses, HIV-1 infected p atients show loss of NK cytotoxic function, down-modulation and/or los s of expression of both CD16 and CD56 surface Ags on NK cells and a gr adual loss of both CD4(+) T cells and NK cell numbers. A potential mec hanism by which these manifestations may occur in vivo was investigate d, 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 e xamined in an in vitro model system, The findings demonstrate that gp1 20-coated peripheral T lymphocytes can serve as targets and are killed in ADCC, Further, the NK cells that recover from the ADCC reaction sh ow a loss of cytotoxic function, acquire the CD16(dim/-) CD56(dim/-) p henotype and a significant fraction is killed by activation-induced ce ll death or apoptosis, These findings are reminiscent of the propertie s of circulating NK cells in HIV-infected patients, The implication of these findings in the pathogenesis of AIDS is discussed.