CD40L+ CD4+ memory T cells migrate in a CD62P-dependent fashion into reactive lymph nodes and license dendritic cells for T cell priming

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 (T(EM)) cells, but not naive or central memory T cells, constitutively expressed CD40L at levels...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2008-10, Vol.205 (11), p.2561-2574
Main Authors: Martín-Fontecha, Alfonso, Baumjohann, Dirk, Guarda, Greta, Reboldi, Andrea, Hons, Miroslav, Lanzavecchia, Antonio, Sallusto, Federica
Format: Article
Language:English
Subjects:
Animals
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD40 Ligand - metabolism
Cell Movement - immunology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Encephalomyelitis, Autoimmune, Experimental - immunology
Flow Cytometry
Immunohistochemistry
Lymph Nodes - immunology
Lymph Nodes - metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
P-Selectin - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 (T(EM)) 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(+) T(EM) 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(+) T(EM) 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(+) T(EM) cell migration into reactive lymph nodes, inhibited DC maturation, T cell priming, and induction of EAE. These results show that T(EM) cells can behave as endogenous adjuvants and suggest a mechanistic link between lymphocyte traffic in lymph nodes and induction of autoimmunity.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20081212