PMID- 21813777
OWN - NLM
STAT- MEDLINE
DCOM- 20111019
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 187
IP  - 5
DP  - 2011 Sep 1
TI  - Physiologic control of IDO competence in splenic dendritic cells.
PG  - 2329-35
LID - 10.4049/jimmunol.1100276 [doi]
AB  - 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-->B7 and PD-1-->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.
FAU - Baban, Babak
AU  - Baban B
AD  - Department of Oral Biology, Georgia Health Sciences University, Augusta, GA 
      30912, USA.
FAU - Chandler, Phillip R
AU  - Chandler PR
FAU - Johnson, Burles A 3rd
AU  - Johnson BA 3rd
FAU - Huang, Lei
AU  - Huang L
FAU - Li, Minghui
AU  - Li M
FAU - Sharpe, Marlon L
AU  - Sharpe ML
FAU - Francisco, Loise M
AU  - Francisco LM
FAU - Sharpe, Arlene H
AU  - Sharpe AH
FAU - Blazar, Bruce R
AU  - Blazar BR
FAU - Munn, David H
AU  - Munn DH
FAU - Mellor, Andrew L
AU  - Mellor AL
LA  - eng
GR  - P01 AI056299/AI/NIAID NIH HHS/United States
GR  - R01 HD041187/HD/NICHD NIH HHS/United States
GR  - P01 CA065493/CA/NCI NIH HHS/United States
GR  - CA096651/CA/NCI NIH HHS/United States
GR  - R37 AI034495/AI/NIAID NIH HHS/United States
GR  - R01 CA103320/CA/NCI NIH HHS/United States
GR  - R01 CA096651/CA/NCI NIH HHS/United States
GR  - AI34495/AI/NIAID NIH HHS/United States
GR  - R01 AI034495/AI/NIAID NIH HHS/United States
GR  - P01 AI 56299/AI/NIAID NIH HHS/United States
GR  - CA72669/CA/NCI NIH HHS/United States
GR  - R01 CA072669/CA/NCI NIH HHS/United States
GR  - P01 CA142106/CA/NCI NIH HHS/United States
GR  - CA103320/CA/NCI NIH HHS/United States
GR  - R01 AI044219/AI/NIAID NIH HHS/United States
GR  - AI63402/AI/NIAID NIH HHS/United States
GR  - AI75165/AI/NIAID NIH HHS/United States
GR  - R37 HL056067/HL/NHLBI NIH HHS/United States
GR  - R01 HL056067/HL/NHLBI NIH HHS/United States
GR  - AI056299/AI/NIAID NIH HHS/United States
GR  - R01 AI063402/AI/NIAID NIH HHS/United States
GR  - HL56067/HL/NHLBI NIH HHS/United States
GR  - R01 CA112431/CA/NCI NIH HHS/United States
GR  - R01 AI075165/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110803
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CpG ODN 1826)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Cell Separation
MH  - Dendritic Cells/cytology/*enzymology/*immunology
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*immunology
MH  - Lymphocyte Activation/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Oligodeoxyribonucleotides/pharmacology
MH  - Spleen/cytology/enzymology/immunology
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - Toll-Like Receptor 9/immunology
PMC - PMC3556270
MID - NIHMS307739
EDAT- 2011/08/05 06:00
MHDA- 2011/10/20 06:00
PMCR- 2013/01/26
CRDT- 2011/08/05 06:00
PHST- 2011/08/05 06:00 [entrez]
PHST- 2011/08/05 06:00 [pubmed]
PHST- 2011/10/20 06:00 [medline]
PHST- 2013/01/26 00:00 [pmc-release]
AID - jimmunol.1100276 [pii]
AID - 10.4049/jimmunol.1100276 [doi]
PST - ppublish
SO  - J Immunol. 2011 Sep 1;187(5):2329-35. doi: 10.4049/jimmunol.1100276. Epub 2011 
      Aug 3.