@article {542206,
	title = {Physiologic control of IDO competence in splenic dendritic cells.},
	journal = {J Immunol},
	volume = {187},
	number = {5},
	year = {2011},
	month = {2011 Sep 1},
	pages = {2329-35},
	abstract = {Dendritic cells (DCs) competent to express the regulatory enzyme IDO in mice are a small but distinctive subset of DCs. Previously, we reported that a high-dose systemic CpG treatment to ligate TLR9 in vivo induced functional IDO exclusively in splenic CD19(+) DCs, which stimulated resting Foxp3-lineage regulatory T cells (Tregs) to rapidly acquire potent suppressor activity. In this paper, we show that IDO was induced in spleen and peripheral lymph nodes after CpG treatment in a dose-dependent manner. Induced IDO suppressed local T cell responses to exogenous Ags and inhibited proinflammatory cytokine expression in response to TLR9 ligation. IDO induction did not occur in T cell-deficient mice or in mice with defective B7 or programmed death (PD)-1 costimulatory pathways. Consistent with these findings, CTLA4 or PD-1/PD-ligand costimulatory blockade abrogated IDO induction and prevented Treg activation via IDO following high-dose CpG treatment. Consequently, CD4(+)CD25(+) T cells uniformly expressed IL-17 shortly after TLR9 ligation. These data support the hypothesis that constitutive interactions from activated T cells or Tregs and IDO-competent DCs via concomitant CTLA4{\textrightarrow}B7 and PD-1{\textrightarrow}PD-ligand signals maintain the default potential to regulate T cell responsiveness via IDO. Acute disruption of these nonredundant interactions abrogated regulation via IDO, providing novel perspectives on the proinflammatory effects of costimulatory blockade therapies. Moreover, interactions between IDO-competent DCs and activated T cells in lymphoid tissues may attenuate proinflammatory responses to adjuvants such as TLR ligands.},
	keywords = {Animals, Antigen Presentation, Cell Separation, Dendritic Cells, Flow Cytometry, Immunohistochemistry, Indoleamine-Pyrrole 2,3,-Dioxygenase, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Transgenic, Oligodeoxyribonucleotides, Spleen, T-Lymphocytes, Regulatory, Toll-Like Receptor 9},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1100276},
	author = {Baban, Babak and Chandler, Phillip R and Johnson, Burles A and Huang, Lei and Li, Minghui and Sharpe, Marlon L and Francisco, Loise M and Sharpe, Arlene H and Blazar, Bruce R and Munn, David H and Mellor, Andrew L}
}
