title: Tolerant T cells display impaired trafficking ability.
abstract: Based on our previous observation that anergic T lymphocytes lose their migratory ability in vitro, we have proposed that anergic T cells are retained in the site where they have been generated to exert their regulatory function. In this study we have analyzed T lymphocyte trafficking and motility following the induction of tolerance in vivo. In a model of non-deletional negative vaccination to xenoantigens in which dendritic cells (DC) localize to specific lymphoid sites depending on the route of administration, tolerant T cells remained localized in the lymph nodes colonized by tolerogenic DC, while primed T cells could traffic efficiently. Using an oral tolerance model that enables the 'tracking' of ovalbumin-specific TCR-transgenic T cells, we confirmed that T cells lose the ability to migrate through syngeneic endothelial cell monolayers following tolerance induction in vivo. Finally, we show that tolerant T cells (both in vitro and ex vivo) can inhibit migration of responsive T cells in an antigen-independent manner. Thus, hyporesponsive T cells localize at the site of tolerance induction in vivo, where they exert their anti-inflammatory properties. In physiological terms, this effect is likely to render immunoregulation a more efficient and controllable event.
authors.affiliation: Department of Immunology, Division of Medicine, Imperial College London, London, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mirenda
authors.forename: Owain
authors.initials: O
authors.lastname: Millington
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
authors.forename: Diane
authors.initials: D
authors.lastname: Scott
authors.forename: Maria P
authors.initials: MP
authors.lastname: Hernandez-Fuentes
authors.forename: Joseph
authors.initials: J
authors.lastname: Read
authors.forename: Peng H
authors.initials: PH
authors.lastname: Tan
authors.forename: Andrew J T
authors.initials: AJ
authors.lastname: George
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
authors.forename: Federica M
authors.initials: FM
authors.lastname: Marelli-Berg
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology* / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology* / Q000502:physiology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D013997:Time Factors
chemical_list: D000941:Antigens; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases