Antigen-driven interactions with dendritic cells and expansion of Foxp3+ regulatory T cells occur in the absence of inflammatory signals.
Foxp3+ regulatory T cells (Tregs) play a pivotal role in the maintenance of peripheral T cell tolerance and are thought to interact with dendritic cells (DC) in secondary lymphoid organs. We analyzed here the in vivo requirements for selective expansion of Ag-specific Treg vs CD4+CD25- effector T cells and engagement of Ag-specific Treg-DC interactions in secondary lymphoid organs. Using i.v. Ag delivery in the absence of inflammation, we found that CD4+CD25+Foxp3+ Tregs undergo vigorous expansion and accumulate whereas naive CD4+CD25-Foxp3- T cells undergo abortive activation. Quantifying directly the interactions between Tregs and CD11c+ DC, we found that Tregs establish cognate contacts with endogenous CD11c+ DC in spleen and lymph nodes at an early time point preceding their expansion. Importantly, we observed that as few as 10(3) Tregs selectively expanded by i.v. Ag injection are able to suppress B and T cell immune responses in mouse recipients challenged with the Ag. Our results demonstrate that Tregs are selectively mobilized by Ag recognition in the absence of inflammatory signals, and can induce thereafter potent tolerance to defined Ag targets.
Chappert
Pascal
P
Genethon, Centre National de la Recherche Scientifique, Unité Mixte de Recherche, 8115, Evry, France.
Leboeuf
Marylène
M
Rameau
Philippe
P
Stockholm
Daniel
D
Liblau
Roland
R
Danos
Olivier
O
Davoust
Jean M
JM
Gross
David-Alexandre
DA
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D039521:CD11c Antigen / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D000941:Antigens; D039521:CD11c Antigen; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006388:Hemagglutinins; D053645:Interleukin-2 Receptor alpha Subunit