Cutting edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent T cell regulatory functions via IFN type 1 signaling

Andrew L. Mellor, Babak Baban, Phillip R. Chandler, Anna Manlapat, David J. Kahler, David H. Munn

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

CpG oligodeoxynucleotides (CpG-ODNs) stimulate innate and adaptive immunity by binding to TLR9 molecules. Paradoxically, expression of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is induced following i.v. CpG-ODN administration to mice. CpG-ODNs induced selective IDO expression by a minor population of splenic CD19+ dendritic cells (DCs) that did not express the plasmacytoid DC marker 120G8. Following CpG-ODN treatment, CD19 + DCs acquired potent IDO-dependent T cell suppressive functions. Signaling through IFN type I receptors was essential for IDO up-regulation, and CpG-ODNs induced selective activation of STAT-1 in CDl9+ DCs. Thus, CpG-ODNs delivered systemically at relatively high doses elicited potent T cell regulatory responses by acting on a discrete, minor population of splenic DCs. The ability of CpG-ODNs to induce both stimulatory and regulatory responses offers novel opportunities for using them as immunomodulatory reagents but may complicate therapeutic use of CpG-ODNs to stimulate antitumor immunity in cancer patients.

Original languageEnglish (US)
Pages (from-to)5601-5605
Number of pages5
JournalJournal of Immunology
Volume175
Issue number9
DOIs
StatePublished - Nov 1 2005

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Oligodeoxyribonucleotides
Regulatory T-Lymphocytes
Oligonucleotides
Dendritic Cells
Adaptive Immunity
Therapeutic Uses
Innate Immunity
Population
Immunity
Up-Regulation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Cutting edge : CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent T cell regulatory functions via IFN type 1 signaling. / Mellor, Andrew L.; Baban, Babak; Chandler, Phillip R.; Manlapat, Anna; Kahler, David J.; Munn, David H.

In: Journal of Immunology, Vol. 175, No. 9, 01.11.2005, p. 5601-5605.

Research output: Contribution to journalArticle

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