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Tolerant t cells display impaired trafficking ability

Mirenda, V. and Millington, O.R. and Lechler, R.I. and Scott, D. and Mernandez-Fuentes, M.P. and Read, J. and Tan, P.H. and George, A.J. and Garside, P. and Marelli-Berg, F.M. (2005) Tolerant t cells display impaired trafficking ability. European Journal of Immunology, 35 (7). pp. 2146-2156. ISSN 0014-2980

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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.