The expression of Fas ligand by macrophages and its upregulation by human immunodeficiency virus infection

Fas/Fas Ligand (FasL) interactions play a significant role in peripheral T lymphocyte homeostasis and in certain pathological states characterized 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. HIV infection of MDM increases FasL protein expression independent of posttranslational mechanisms, thus highlighting the virus-induced transcriptional upregulation of Fast, The in vitro relevance of these observations 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 situ hybridization, The degree of Fast protein expression in vivo correlates with the degree of tissue apoptosis (r = 0.761, P < 0.001), which 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 potential role of Fast expression in the immunopathogenesis of HIV infection.