Primary cytotoxicity against the envelope glycoprotein of human immunodeficiency virus-1: evidence for antibody-dependent cellular cytotoxicity in vivo.

Fresh peripheral blood mononuclear cells from human immunodeficiency virus-1 (HIV-1) seropositive donors can lyse target cells expressing the envelope glycoprotein in vitro. In most cases, this antigen-specific lysis is not mediated by T lymphocytes. Lymphoblastoid cell lines infected with recombinant vaccinia viruses expressing different forms of the envelope protein of HIV-1 were used as target cells in chromium-release assays of primary cytotoxic effector cells and of antibody-dependent cellular cytotoxicity (ADCC). By depleting effector cells of CD16+ lymphocytes, or by blocking target cell lysis with an anti-human IgG serum, primary env-specific lysis was found to be due to ADCC, the effector cells being armed in vivo with specific, cytophilic antibodies. This phenomenon is dependent on cell surface expression of the envelope protein and is directed against both gp120 and gp41. Human HIV-1 antibody-positive sera are able to mediate ADCC against HIV-infected CD4+ T lymphocytes, suggesting a possible role of ADCC in the natural infection.