Complement-induced regulatory T cells suppress T-cell responses but allow for dendritic-cell maturation.
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.
Barchet
Winfried
W
Washington University School of Medicine, Department of Pathology and Immunology, St Louis, MO 63110, USA.
Price
Jeffrey D
JD
Cella
Marina
M
Colonna
Marco
M
MacMillan
Sandra K
SK
Cobb
J Perren
JP
Thompson
Paul A
PA
Murphy
Kenneth M
KM
Atkinson
John P
JP
Kemper
Claudia
C
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*
D015703:Antigens, CD; D016753:Interleukin-10; D023201:CD40 Ligand; D003165:Complement System Proteins