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 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.
Martín-Fontecha
Alfonso
A
Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland. alfonso.martin-fontecha@kcl.ac.uk
Baumjohann
Dirk
D
Guarda
Greta
G
Reboldi
Andrea
A
Hons
Miroslav
M
Lanzavecchia
Antonio
A
Sallusto
Federica
F
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism*
D019007:P-Selectin; D023201:CD40 Ligand