PMID- 10725715
OWN - NLM
STAT- MEDLINE
DCOM- 20000504
LR  - 20220321
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 164
IP  - 7
DP  - 2000 Apr 1
TI  - Indoleamine 2,3-dioxygenase production by human dendritic cells results in the 
      inhibition of T cell proliferation.
PG  - 3596-9
AB  - Dendritic cells (DCs) play a key role in the activation and regulation of B and T 
      lymphocytes. Production of indoleamine 2, 3-dioxygenase (IDO) by macrophages has 
      recently been described to result in inhibition of T cell proliferation through 
      tryptophan degradation. Since DCs can be derived from monocytes, we sought to 
      determine whether DCs could produce IDO which could potentially regulate T cell 
      proliferation. Northern blot analysis of RNA from cultured monocyte-derived human 
      DC revealed that IDO mRNA was induced upon activation with CD40 ligand and 
      IFN-gamma. IDO produced from activated DCs was functionally active and capable of 
      metabolizing tryptophan to kynurenine. Activated T cells were also capable of 
      inducing IDO production by DCs, which was inhibited by a neutralizing Ab against 
      IFN-gamma. DC production of IDO resulted in inhibition of T cell proliferation, 
      which could be prevented using the IDO inhibitor 1-methyl-dl -tryptophan. These 
      results suggest that activation of DCs induces the production of functional IDO, 
      which causes depletion of tryptophan and subsequent inhibition of T cell 
      proliferation. This may represent a potential mechanism for DCs to regulate the 
      immune response.
FAU - Hwu, P
AU  - Hwu P
AD  - Surgery Branch, Division of Clinical Sciences, National Cancer Institute, 
      Bethesda, MD 20892, USA.
FAU - Du, M X
AU  - Du MX
FAU - Lapointe, R
AU  - Lapointe R
FAU - Do, M
AU  - Do M
FAU - Taylor, M W
AU  - Taylor MW
FAU - Young, H A
AU  - Young HA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Drug Combinations)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 343-65-7 (Kynurenine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 8DUH1N11BX (Tryptophan)
RN  - EC 1.13.11.11 (Tryptophan Oxygenase)
SB  - IM
MH  - CD40 Ligand
MH  - Cell Communication/immunology
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid
MH  - Coculture Techniques
MH  - Dendritic Cells/*enzymology/*immunology
MH  - Drug Combinations
MH  - Humans
MH  - *Immune Tolerance
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase
MH  - Interferon-gamma/pharmacology
MH  - Kynurenine/isolation & purification/metabolism
MH  - Ligands
MH  - Lipopolysaccharides/pharmacology
MH  - Lymphocyte Activation/*immunology
MH  - Membrane Glycoproteins/pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - T-Lymphocytes/*immunology
MH  - Tryptophan/metabolism
MH  - Tryptophan Oxygenase/*biosynthesis/genetics/physiology
MH  - Tumor Cells, Cultured
EDAT- 2000/03/22 09:00
MHDA- 2000/05/08 09:00
CRDT- 2000/03/22 09:00
PHST- 2000/03/22 09:00 [pubmed]
PHST- 2000/05/08 09:00 [medline]
PHST- 2000/03/22 09:00 [entrez]
AID - ji_v164n7p3596 [pii]
AID - 10.4049/jimmunol.164.7.3596 [doi]
PST - ppublish
SO  - J Immunol. 2000 Apr 1;164(7):3596-9. doi: 10.4049/jimmunol.164.7.3596.