Functional dichotomy of plasmacytoid dendritic cells: antigen-specific activation of T cells versus production of type I interferon.
Human plasmacytoid dendritic cells (PDC) are believed to link innate and adaptive immunity by producing type I interferon (IFN-I) and triggering adaptive T cell-mediated immunity. However, it remains elusive to which degree both PDC functions are linked. Here we show that CMV antigen targeted to PDC using a CD303 (blood dendritic cell antigen 2, BDCA-2) mAb is rapidly endocytosed and traffics via early sorting endosomes to emerging MHC-enriched compartments. Both processes occur independently of TLR ligand stimulation. Restimulation of CMV-specific CD4(+) effector-memory T helper cells by autologous PDC and induction of IFN-I production in PDC are dependent on appropriate stimulation. Type B CpG oligonucleotide (CpG-B)-stimulated PDC efficiently process and present CMV antigen and are thus capable of stimulating CMV-specific effector-memory T helper cells. CpG-A-stimulated PDC produce large amounts of IFN-I and express programmed death receptor-1 ligand 1. CpG-A plus CpG-B-co-stimulated PDC behave like CpG-B-stimulated PDC, suggesting that antigen processing and presentation in PDC is dependent on stimulation that concurrently inhibits IFN-I production. In vivo targeting of antigens to PDC via CD303 combined with appropriate PDC stimulation may allow induction of specific T cell activation.
Jaehn
Peter S
PS
Department of Research and Development, Miltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, Bergisch Gladbach, Germany. peterj@miltenyibiotec.de
Zaenker
Kurt S
KS
Schmitz
Juergen
J
Dzionek
Andrzej
A
D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003587:Cytomegalovirus / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011971:Receptors, Immunologic
D000956:Antigens, Viral; C443299:CLEC4C protein, human; C408982:CPG-oligonucleotide; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic