title: Specific deletion of autoreactive T cells by adenovirus-transfected, Fas ligand-producing antigen-presenting cells.
abstract: Immune privilege is a unique strategy developed in several internal organs that can prevent the development of immune attack against these vital organs. One critical mechanism of immune privilege is utilization of Fas/FasL-mediated apoptosis to delete the invading T cells at the immune privilege sites. In this article, we describe the development and application of a unique cell-gene therapy to correct defective FasL-mediated apoptosis and autoimmune disease in autoimmune mice. This cell-gene therapy strategy using antigen-presenting cells (APCs) to express FasL is not only a therapeutic tool, but also has allowed us to understand the complexity of T cell regulation and the concept of eliminating T cells in the spleen, lymph node, or elsewhere in vivo to regulate the homeostasis of the peripheral T cell response. In this regard, the FasL-expressing APCs can be considered as circulating and regulatable immune privilege sites. Our studies provide substantial evidence that FasL-expressing APCs can be introduced exogenously without liver toxicity to eliminate infiltrating T cells and prevent the development of immune attack in lung, liver, kidney, joint, and salivary gland. Therefore, given the hazardous potential of persistent T cell invasion at the local inflammatory site, it is tempting to speculate that such an endogenous control mechanism occurs normally in vivo to limit a chronic T cell inflammatory response.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 35294, USA.
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhan
authors.forename: John D
authors.initials: JD
authors.lastname: Mountz
authors.forename: Martin
authors.initials: M
authors.lastname: Fleck
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Hsu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D017209:Apoptosis; D015551:Autoimmunity; D053222:Fas Ligand Protein; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014162:Transfection; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor