PT  - JOURNAL ARTICLE
AU  - Mellor, Andrew L.
AU  - Baban, Babak
AU  - Chandler, Phillip R.
AU  - Manlapat, Anna
AU  - Kahler, David J.
AU  - Munn, David H.
TI  - Cutting Edge: CpG Oligonucleotides Induce Splenic CD19<sup>+</sup> Dendritic Cells to Acquire Potent Indoleamine 2,3-Dioxygenase-Dependent T Cell Regulatory Functions via IFN Type 1 Signaling
AID  - 10.4049/jimmunol.175.9.5601
DP  - 2005 Nov 01
TA  - The Journal of Immunology
PG  - 5601--5605
VI  - 175
IP  - 9
4099  - http://www.jimmunol.org/content/175/9/5601.short
4100  - http://www.jimmunol.org/content/175/9/5601.full
SO  - J. Immunol.2005 Nov 01; 175
AB  - 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 CD19+ 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.