B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase

A discrete population of splenocytes with attributes of dendritic cells (DCs) and coexpressing the B-cell marker CD19 is uniquely competent to express the T-cell regulatory enzyme indoleamine 2,3-dioxygenase (IDO) in mice treated with TLR9 ligands (CpGs). Here we show that IDO-competent cells expres...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2010-06, Vol.107 (23), p.10644-10648
Hauptverfasser: Johnson, Burles A. III, Kahler, David J, Baban, Babak, Chandler, Phillip R, Kang, Baolin, Shimoda, Michiko, Koni, Pandelakis A, Pihkala, Jeanene, Vilagos, Bojan, Busslinger, Meinrad, Munn, David H, Mellor, Andrew L
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Sprache:eng
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Zusammenfassung:A discrete population of splenocytes with attributes of dendritic cells (DCs) and coexpressing the B-cell marker CD19 is uniquely competent to express the T-cell regulatory enzyme indoleamine 2,3-dioxygenase (IDO) in mice treated with TLR9 ligands (CpGs). Here we show that IDO-competent cells express the B-lineage commitment factor Pax5 and surface immunoglobulins. CD19 ablation abrogated IDO-dependent T-cell suppression by DCs, even though cells with phenotypic attributes matching IDO-competent cells developed normally and expressed IDO in response to interferon γ. Consequently, DCs and regulatory T cells (Tregs) did not acquire T-cell regulatory functions after TLR9 ligation, providing an alternative perspective on the known T-cell regulatory defects of CD19-deficient mice. DCs from B-cell-deficient mice expressed IDO and mediated T-cell suppression after TLR9 ligation, indicating that B-cell attributes were not essential for B-lymphoid IDO-competent cells to regulate T cells. Thus, IDO-competent cells constitute a distinctive B-lymphoid cell type with quintessential T-cell regulatory attributes and phenotypic features of both B cells and DCs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0914347107