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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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IMMUNOBIOLOGY

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. Perren Cobb, Paul A. Thompson, Kenneth M. Murphy, John P. Atkinson, and Claudia Kemper

From the Department of Pathology and Immunology, the Graduate Program in Immunology, the Department of Surgery, the Division of Biostatistics, and the Division of Rheumatology, Washington University School of Medicine, St Louis, MO.

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.


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