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 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 gamma. 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.
Johnson
Burles A
BA
Immunotherapy and Cancer Centers, Departments of Pathology and Medicine, and Flow Cytometry Core Facility, Medical College of Georgia, Augusta, GA 30912, USA.
Kahler
David J
DJ
Baban
Babak
B
Chandler
Phillip R
PR
Kang
Baolin
B
Shimoda
Michiko
M
Koni
Pandelakis A
PA
Pihkala
Jeanene
J
Vilagos
Bojan
B
Busslinger
Meinrad
M
Munn
David H
DH
Mellor
Andrew L
AL
D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D019070:Cell Lineage; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051757:PAX5 Transcription Factor / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology
D018941:Antigens, CD19; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9