Tolerant T cells display impaired trafficking ability.
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.
Mirenda
Vincenzo
V
Department of Immunology, Division of Medicine, Imperial College London, London, UK.
Millington
Owain
O
Lechler
Robert I
RI
Scott
Diane
D
Hernandez-Fuentes
Maria P
MP
Read
Joseph
J
Tan
Peng H
PH
George
Andrew J T
AJ
Garside
Paul
P
Marelli-Berg
Federica M
FM
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
D000941:Antigens; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases