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CORRESPONDENCE Federica Sallusto: federica.sallusto{at}irb.unisi.ch OR Alfonso Martín-Fontecha: alfonso.martin-fontecha{at}kcl.ac.uk
There is growing evidence that the maturation state of dendritic cells (DCs) is a critical parameter determining the balance between tolerance and immunity. We report that mouse CD4+ effector memory T (TEM) cells, but not naive or central memory T cells, constitutively expressed CD40L at levels sufficient to induce DC maturation in vitro and in vivo in the absence of antigenic stimulation. CD4+ TEM cells were excluded from resting lymph nodes but migrated in a CD62P-dependent fashion into reactive lymph nodes that were induced to express CD62P, in a transient or sustained fashion, on high endothelial venules. Trafficking of CD4+ TEM cells into chronic reactive lymph nodes maintained resident DCs in a mature state and promoted naive T cell responses and experimental autoimmune encephalomyelitis (EAE) to antigens administered in the absence of adjuvants. Antibodies to CD62P, which blocked CD4+ TEM cell migration into reactive lymph nodes, inhibited DC maturation, T cell priming, and induction of EAE. These results show that TEM cells can behave as endogenous adjuvants and suggest a mechanistic link between lymphocyte traffic in lymph nodes and induction of autoimmunity.
A. Martín-Fontecha's present address is Dept. of Nephrology and Transplantation, King's College London and Guy's and St Thomas' Hospital, SE1 9RT London, England, UK.
G. Guarda's present address is Dept. of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
M. Hons's present address is Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
© 2008 Martín-Fontecha et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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