title: Complement-induced regulatory T cells suppress T-cell responses but allow for dendritic-cell maturation.
abstract: Concurrent activation of the T-cell receptor (TCR) and complement regulator CD46 on human CD4+ T lymphocytes induces Tr1-like regulatory T cells that suppress through IL-10 secretion bystander T-cell proliferation. Here we show that, despite their IL-10 production, CD46-induced T-regulatory T cells (Tregs) do not suppress the activation/maturation of dendritic cells (DCs). DC maturation by complement/CD46-induced Tregs is mediated through simultaneous secretion of GM-CSF and soluble CD40L, factors favoring DC differentiation and reversing inhibitory effects of IL-10. Thus, CD46-induced Tregs produce a distinct cytokine profile that inhibits T-cell responses but leaves DC activation unimpaired. Such "DC-sparing" Tregs could be desirable at host/environment interfaces such as the gastrointestinal tract where their specific cytokine profile provides a mechanism that ensures unresponsiveness to commensal bacteria while maintaining reactivity to invading pathogens.
authors.affiliation: Washington University School of Medicine, Department of Pathology and Immunology, St Louis, MO 63110, USA.
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Price
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Sandra K
authors.initials: SK
authors.lastname: MacMillan
authors.forename: J Perren
authors.initials: JP
authors.lastname: Cobb
authors.forename: Paul A
authors.initials: PA
authors.lastname: Thompson
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: Claudia
authors.initials: C
authors.lastname: Kemper
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016753:Interleukin-10; D023201:CD40 Ligand; D003165:Complement System Proteins