title: Molecular and cellular mechanisms regulating T and B cell apoptosis through Fas/FasL interaction.
abstract: Fas (CD95) and Fas ligand (FasL) are a receptor/ligand pair critically involved in lymphocyte homeostasis and peripheral tolerance such that genetic defect in either Fas or FasL results in an autoimmune lymphoproliferative syndrome. Fas is a type I transmembrane protein and a member of the tumor necrosis factor receptor (TNFR) family whereas FasL is a type II transmembrane protein and a member of TNF family. Binding of Fas by FasL induces apoptosis of the Fas-expressing cells. In the past few years, Fas/FasL interaction has been connected to a series of important phenomena previously viewed as independent immune processes. The activation-induced T cell death (AICD) and the FasL-mediated cytotoxicity by activated T cells are two critical mechanisms that can account for most of these phenomena. It is in the context of the two mechanisms that we discuss in this review the molecular and cellular events that occur during T/T and T/B interactions that account for the down-regulation of the immune response. We have also discussed recent advances in the areas of FasL gene regulation, lymphokine regulation of AICD, and regulation of B cell susceptibility to FasL. Investigation in these areas should help elucidate the role of Fas/FasL in the complex network of regulatory mechanisms that control immune response and autoimmunity.
authors.affiliation: Department of Medicine, Boston University School of Medicine, MA 02118, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Ju
authors.forename: K
authors.initials: K
authors.lastname: Matsui
authors.forename: M
authors.initials: M
authors.lastname: Ozdemirli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D053222:Fas Ligand Protein; D006801:Humans; D007109:Immunity; D008562:Membrane Glycoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D019014:fas Receptor / Q000276:immunology*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor