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.

journal_name

Blood

journal_title

Blood

authors

Barchet W,Price JD,Cella M,Colonna M,MacMillan SK,Cobb JP,Thompson PA,Murphy KM,Atkinson JP,Kemper C

doi

10.1182/blood-2005-07-2951

subject

Has Abstract

pub_date

2006-02-15 00:00:00

pages

1497-504

issue

4

eissn

0006-4971

issn

1528-0020

pii

2005-07-2951

journal_volume

107

pub_type

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