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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1497-1504.
Prepublished online as a Blood First Edition Paper on October 20, 2005; DOI 10.1182/blood-2005-07-2951.
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Submitted July 22, 2005
Accepted October 6, 2005
Complement-induced regulatory T cells suppress T cell responses but allow for dendritic cell maturation
Winfried Barchet, Jeffrey D Price, Marina Cella, Marco Colonna, Sandra K MacMillan, J P Cobb, Paul A Thompson, Kenneth M Murphy, John P Atkinson, and Claudia Kemper*
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Graduate Program in Immunology, Washington University School of Medicine, St. Louis, MO, USA
Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, USA
* Corresponding author; email: ckemper{at}im.wustl.edu.
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 Tregs do not suppress the activation/maturation of dendritic cells (DC). 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 like the gastrointestinal tract where their specific cytokine profile provides a mechanism that ensures unresponsiveness to commensal bacteria while maintaining reactivity to invading pathogens.

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