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

AL Mellor, B Baban, PR Chandler… - The Journal of …, 2005 - journals.aai.org
AL Mellor, B Baban, PR Chandler, A Manlapat, DJ Kahler, DH Munn
The Journal of Immunology, 2005journals.aai.org
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 iv 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 …
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 iv 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.
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