EVIDENCE FOR A DEFECT OF ANTIBODY-DEPENDENT CELLULAR CYTOTOXIC (ADCC)EFFECTOR FUNCTION AND ANTI-HIV GP120 41-SPECIFIC ADCC-MEDIATING ANTIBODY-TITERS IN HIV-INFECTED INDIVIDUALS/

Antibody-dependent cellular cytotoxicity (ADCC) is an important antivi ral effector mechanism. However, its role, as well as the functional i ntegrity of the ADCC-effector cells in HIV infections, is not well und erstood. For studying gp120/41-specific ADCC, we recently developed a virus-free target cell system, using a natural killer (NK) cell activi ty-resistant human lymphoid cell line of B lineage, which was transfec ted with the env gene of the human immunodeficiency virus type 1 (HIV- 1); gp120/41-expressing cell clones were thus selected. In this study, these gp120/41-expressing cloned cells were used as targets in a gp12 0/41-specific ADCC assay for (a) examining the functional integrity of ADCC-effector cells from HIV-seropositive individuals, and (b) titrat ing the sera of these individuals for gpl20/41-specific, ADCC-mediatin g antibodies. Our data indicate for the first time that the percentage of sera positive for ADCC-mediating antibodies to gp120/41 is higher in individuals with CD4 counts less than or equal to 400 and greater t han or equal to 200/mm(3). The individuals with CD4 counts <200/mm(3) were found to have the lowest titers of these antibodies in their sera . The ADCC-effector function of the peripheral blood mononuclear cells (PBMC) of HIV-infected individuals was significantly (p < 0.05) reduc ed as compared to the PBMC from healthy, HIV-seronegative individuals. Further, human recombinant IL2 and interferon-gamma were found to exe rt a significant (p < 0.05) enhancing effect on ADCC mediated by PBMC from these HIV-infected individuals. We also show that two virus neutr alizing, gp120-specific mouse monoclonal antibodies 0.5P beta and 902 were unable to mediate ADCC as well as to block the ADCC mediated by t he AIDS patients' sera. Further, these results suggest that the presen t gp120/41-expressing target cell system might prove very useful in co nducting large-scale studies on both gpl20/41-specific ADCC-effector f unction of peripheral blood mononuclear cells and ADCC-mediating antib ody responses in different types of HIV-positive individuals.