Role of antibody-dependent cellular cytotoxicity and lymphokine-activated killer cells in AIDS and related diseases.

This overview summarizes current knowledge on the overall efficacy and potential contribution of antibody-dependent cellular cytotoxicity (ADCC) and lymphokine-activated killer cell (LAK) activities in evoking non-major histocompatibility complex (non-MHC) cytolytic responses to human immunodeficiency virus-1 (HIV-1)-infected targets. High titers of ADCC antibodies to the HIV-1 virion are present in HIV-1-seropositive populations at all stages of disease. These antibodies are broadly reactive with a large number of HIV-1 strains and are predominantly directed against envelope determinants spanning both gp120 and gp41. However, the relative ability of natural killer (NK) effectors, derived from HIV-seropositive individuals, to evoke ADCC responses becomes increasingly impaired with disease progression. HIV-1-seropositive individuals also show marked decreases in both production of and responsiveness to interleukin-2 (IL-2). HIV-1-seropositive individuals generally have the ability to generate ex vivo propagated LAK cells; however, these cytolytic effectors are less effective than their counterparts derived from healthy controls. Increased understanding and control of non-MHC-restricted cytotoxic-responses to HIV, and their induction by lymphokines, may lead to improved treatment strategies for the management of AIDS and related diseases.