FAS LIGAND DEFICIENCY IN HIV DISEASE

Apoptosis is postulated to be involved as an anti-viral immune mechani sm by killing infected cells before viral replication has occurred, Th e Fas-Fas ligand interaction is a powerful regulator of T cell apoptos is and could potentially act as a potent anti-viral immune mechanism a gainst T cell tropic virus such as human immunodeficiency virus (HIV), We investigated the status of Fas ligand in peripheral blood mononucl ear cells (PBMCs) obtained from persons infected with HIV. We found th at monocytes in freshly isolated PBMCs from healthy individuals posses s cell surface Fas ligand, In contrast, monocytes in freshly isolated PBMCs from HIV-infected patients had no detectable Fas ligand on the c ell surface. Consistent with these findings of surface expression, Fas ligand activity was deficient in the cells from HIV-infected persons. The effect of replacing Fas ligand activity on HIV production by pati ents' cells was assessed in an in vitro assay. The addition of a funct ional anti-Fas antibody to PBMCs from HIV-infected individuals inhibit ed viral production by greater than 90% without affecting lymphocytic function. These findings suggest the possibility of a new therapeutic modality for the treatment of HIV-infected individuals based on the re constitution of Fas ligand activity.