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, Claudia Kemper

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish
Pages (from-to)1497-1504
Number of pages8
JournalBlood
Volume107
Issue number4
DOIs
StatePublished - Feb 15 2006

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