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Human Plasmacytoid Dendritic Cells Activated by CpG Oligodeoxynucleotides Induce the Generation of CD4+CD25+ Regulatory T Cells

Authors :
Wei Chen
Yong-Jun Liu
Arthur M. Krieg
Bruce R. Blazar
Xueqing Liang
Angela Panoskaltsis-Mortari
Amanda J. Dawson
E. Ashley Moseman
Source :
The Journal of Immunology. 173:4433-4442
Publication Year :
2004
Publisher :
The American Association of Immunologists, 2004.

Abstract

Plasmacytoid dendritic cells (PDCs) are key effectors in host innate immunity and orchestrate adaptive immune responses. CpG oligodeoxynucleotides (ODN) have potent immunostimulatory effects on PDCs through TLR9 recognition and signaling. Little is known about the effects of CpG ODN on human PDC-mediated T cell priming. Here we show that type B CpG ODN effectively promotes PDCs to prime allogeneic naive CD4+CD25− T cells to differentiate into CD4+CD25+ regulatory T (Treg) cells. The CD4+CD25+ T cells induced by CpG ODN-activated PDCs express forkhead transcription factor 3 and produce IL-10, TGF-β, IFN-γ, and IL-6, but low IL-2 and IL-4. These CD4+CD25+ T cells are hyporesponsive to secondary alloantigen stimulation and strongly inhibit proliferation of autologous or allogeneic naive CD4+ T cells in an Ag-nonspecific manner. CpG ODN-activated PDCs require direct contact with T cells to induce CD4+CD25+ Treg cells. Interestingly, IL-10 and TGF-β were undetectable in the supernatants of CpG ODN-stimulated PDC cultures. Both CpG-A and CpG-C ODN-activated PDCs similarly induced the generation of CD4+CD25+ Treg cells with strong immune suppressive function. This study demonstrates that TLR9 stimulation can promote PDC-mediated generation of CD4+CD25+ Treg cells and suggests PDCs may play an important role in the maintenance of immunological tolerance.

Details

ISSN :
15506606 and 00221767
Volume :
173
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi.dedup.....d5ecbea851feefd82db815c5e87a3e56
Full Text :
https://doi.org/10.4049/jimmunol.173.7.4433