Expansion of peripheral naturally occurring T regulatory cells by Fms-like tyrosine kinase 3 ligand treatment.
نویسندگان
چکیده
Fms-like tyrosine kinase 3 ligand (FLT3L) plays a major role in dendritic cell (DC) biology. Deficiency of FLT3L causes a dramatic decrease in DC numbers, whereas increasing its availability (by repetitive injections for 7-10 days) leads to a 10-fold increase in DC numbers. In this study, we show that FLT3L treatment indirectly leads to an expansion of peripheral naturally occurring T regulatory cells (NTregs). The FLT3L-induced increase in NTregs was still observed in thymectomized mice, ruling out the role of the thymus in this mechanism. Instead, the increased number of NTregs was due to proliferation of preexisting NTregs, most likely due to favored interactions with increased number of DCs. In vitro, we show that DCs induce regulatory T-cell (Treg) proliferation by direct cell contact and in an interleukin-2-dependent, T-cell receptor-independent manner. FLT3L could prevent death induced by acute graft-versus-host disease (GVHD). This study demonstrates unique aspects in the regulation of Treg homeostasis by DCs, which were unappreciated until now. It also reinforces the relevance of FLT3L treatment in GVHD by its ability to increase both the number of tolerizing DCs and NTregs.
منابع مشابه
Plenary paper Expansion of peripheral naturally occurring T regulatory cells by Fms-like tyrosine kinase 3 ligand treatment
1Departement Biomedizin Basel, Division of Molecular Immunology, University of Basel, Basel, Switzerland; 2Centre d’Immunologie de Marseille-Luminy, Université de la Méditerrannée, Inserm Unité 631, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 6102, Marseille, France; and 3Inserm Unité 645, Université Franche-Comté, Etablissement Français du Sang, Bourgogne...
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عنوان ژورنال:
- Blood
دوره 113 25 شماره
صفحات -
تاریخ انتشار 2009