ANALYSIS OF THE CYTOLYTIC ACTIVITY MEDIATED BY NATURAL-KILLER-CELLS FROM ACQUIRED-IMMUNODEFICIENCY-SYNDROME PATIENTS IN RESPONSE TO PHYTOHEMAGGLUTININ OR ANTI-CD16 MONOCLONAL-ANTIBODY

The aim of this study was to assess the cytolytic potential of natural killer (NK) cells from human immunodeficiency virus type 1 (HIV-1)-infected patients, at different stages of the disease. Twenty HIV-1 seronegative donors as well as sixty HIV-1 seropositive patients were studied. Phytohemagglutinin and/or the anti-CD16 monoclonal antibody Kd1 were used to redirect the peripheral blood lymphocyte lysis of these patients to the Cr-51-labeled Fc gamma receptor-positive P815 murine mastocytoma target cell line. In parallel, NK cytotoxicity to tumor targets was investigated. Seronegative as well as HIV-1 Center for Disease Control (CDC) stage II patients showed maintained cytolytic activity. The cytolytic potential declined with disease progression, starting with CDC IVC2 patients, and was strongly diminished in acquired immunodeficiency syndrome stage patients. This defect was accompanied by decreased cytolytic activity to tumor targets and was not corrected by the in vitro addition of interleukin-2. The number of cells bearing a mature NK phenotype was normal in all the study groups. Our data suggest that the impaired NK cytotoxicity to tumor targets described during the progression of HIV-1 disease may be related to the progressive loss of function of surface receptors involved in NK cell triggering.