Functional plasticity of dendritic cell subsets as mediated by CD40 versus B7 activation.
Murine dendritic cells (DCs) can present Ag in an immunogenic or tolerogenic fashion, the distinction depending on either the occurrence of specialized DC subsets or the maturation or activation state of the DC. Although DC subsets may be programmed to direct either tolerance or immunity, it is not known whether appropriate environmental stimulation can result in complete flexibility of a basic program. Using splenic CD8(-) and CD8(+) DCs that mediate the respective immunogenic and tolerogenic presentation of self peptides, we show that both the in vivo and in vitro activities of either subset can be altered by ligation of specific surface receptors. Otherwise immunogenic CD8(-) DCs become tolerogenic upon B7 ligation by soluble CTLA-4, a maneuver that initiates immunosuppressive tryptophan catabolism. In contrast, CD40 ligation on tolerogenic CD8(+) DCs makes these cells capable of immunogenic presentation. Thus, environmental conditioning by T cell ligands may alter the default function of DC subsets to meet the needs of flexibility and redundancy.
Grohmann
Ursula
U
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy.
Bianchi
Roberta
R
Orabona
Ciriana
C
Fallarino
Francesca
F
Vacca
Carmine
C
Micheletti
Alessandra
A
Fioretti
Maria C
MC
Puccetti
Paolo
P
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000943:Antigens, Differentiation / Q000378:metabolism / Q000494:pharmacology; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016827:CD8 Antigens / Q000096:biosynthesis / Q000378:metabolism; D060908:CTLA-4 Antigen; D002999:Clone Cells; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016827:CD8 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D007166:Immunosuppressive Agents; D008024:Ligands; D008562:Membrane Glycoproteins; D014364:Tryptophan