title: Chronic exposure to low levels of antigen in the periphery causes reversible functional impairment correlating with changes in CD5 levels in monoclonal CD8 T cells.
abstract: This study describes a double-transgenic model in which monoclonal CD8 F5 T cells are chronically exposed to self Ag (nucleoprotein) in the periphery, but are not affected during thymic development. Chronic exposure of CD8 T cells to their cognate Ag rendered them unable to proliferate or produce cytokines in response to antigenic stimulation in vitro. However, the cells still retained some killer function in vivo and continuously eliminated APC expressing high levels of Ag. In addition, when crossed with mice expressing Ag in the anterior pituitary gland (triple-transgenic mice), F5 T cells migrated to this site and killed growth hormone producing somatotrophs. The anergic state was reversible upon transfer into Ag-free recipients, resulting in full recovery of in vitro responsiveness to Ag. Anergic CD8 T cells express higher levels of CD5, a negative regulator of T cell signaling, whereas after transfer and residence in Ag-free hosts, CD5 levels returned to normal. This suggests that up-regulation of negative T cell regulators in peripheral T cells exposed to chronic stimulation by Ag may prevent full functionality and thus avoid overt autoreactivity.
authors.affiliation: Division of Molecular Immunology, The National Institute for Medical Research, London, United Kingdom.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Stamou
authors.forename: James
authors.initials: J
authors.lastname: de Jersey
authors.forename: Danielle
authors.initials: D
authors.lastname: Carmignac
authors.forename: Clio
authors.initials: C
authors.lastname: Mamalaki
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kioussis
authors.forename: Brigitta
authors.initials: B
authors.lastname: Stockinger
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D018956:CD5 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics; D002999:Clone Cells; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016601:RNA-Binding Proteins; D011828:Radiation Chimera / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D001324:Autoantigens; D018956:CD5 Antigens; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins