title: Loss of the death receptor CD95 (Fas) expression by dendritic cells protects from a chronic viral infection.
abstract: Chronic viral infections incapacitate adaptive immune responses by "exhausting" virus-specific T cells, inducing their deletion and reducing productive T-cell memory. Viral infection rapidly induces death receptor CD95 (Fas) expression by dendritic cells (DCs), making them susceptible to elimination by the immune response. Lymphocytic choriomeningitis virus (LCMV) clone 13, which normally establishes a chronic infection, is rapidly cleared in C57Black6/J mice with conditional deletion of Fas in DCs. The immune response to LCMV is characterized by an extended survival of virus-specific effector T cells. Moreover, transfer of Fas-negative DCs from noninfected mice to preinfected animals results in either complete clearance of the virus or a significant reduction of viral titers. Thus, DC-specific Fas expression plays a role in regulation of antiviral responses and suggests a strategy for stimulation of T cells in chronically infected animals and humans to achieve the clearance of persistent viruses.
authors.affiliation: Department of Pathology and Committee on Immunology, and.
authors.forename: Vineeth
authors.initials: V
authors.lastname: Varanasi
authors.affiliation: Institute for Genomics and Systems Biology and Department of Human Genetics, The University of Chicago, Chicago, IL 60637.
authors.forename: Aly Azeem
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Department of Pathology and Committee on Immunology, and achervon@bsd.uchicago.edu.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chervonsky
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D017353:Gene Deletion; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014709:Vero Cells; D019014:fas Receptor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D019014:fas Receptor