THE EXPRESSION OF FAS LIGAND BY MACROPHAGES AND ITS UP-REGULATION BY HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Fas/Fas Ligand (FasL) interactions play a significant role in peripher al T lymphocyte homeostasis and in certain pathological states charact erized by T cell depletion. In this study, we demonstrate that antigen -presenting cells such as monocyte-derived human macrophages (MDM) but not monocyte-derived dendritic cells express basal levels of FasL. HI V infection of MDM increases FasL protein expression independent of po sttranslational mechanisms, thus highlighting the virus-induced transc riptional upregulation of Fast, The in vitro relevance of these observ ations is confirmed in human lymphoid tissue, FasL protein expression is constitutive and restricted to tissue macrophages and not dendritic cells, Moreover, a significant increase in macrophage-associated Fast is observed in lymphoid tissue from HIV (+) individuals (P < 0.001), which is further supported by increased levels of Fast mRNA using in s itu hybridization, The degree of Fast protein expression in vivo corre lates with the degree of tissue apoptosis (r = 0.761, P < 0.001), whic h is significantly increased in tissue from HIV-infected patients (P < 0.001), These results identify human tissue macrophages as a relevant source for Fast expression in vitro and in vivo and highlight the pot ential role of Fast expression in the immunopathogenesis of HIV infect ion.