PMID- 15254595
OWN - NLM
STAT- MEDLINE
DCOM- 20040831
LR  - 20211203
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 114
IP  - 2
DP  - 2004 Jul
TI  - Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in 
      tumor-draining lymph nodes.
PG  - 280-90
AB  - One mechanism contributing to immunologic unresponsiveness toward tumors may be 
      presentation of tumor antigens by tolerogenic host APCs. We show that mouse 
      tumor-draining LNs (TDLNs) contained a subset of plasmacytoid DCs (pDCs) that 
      constitutively expressed immunosuppressive levels of the enzyme indoleamine 
      2,3-dioxygenase (IDO). Despite comprising only 0.5% of LN cells, these pDCs in 
      vitro potently suppressed T cell responses to antigens presented by the pDCs 
      themselves and also, in a dominant fashion, suppressed T cell responses to 
      third-party antigens presented by nonsuppressive APCs. Adoptive transfer of DCs 
      from TDLNs into naive hosts created profound local T cell anergy, specifically 
      toward antigens expressed by the transferred DCs. Anergy was prevented by 
      targeted disruption of the IDO gene in the DCs or by administration of the IDO 
      inhibitor drug 1-methyl-D-tryptophan to recipient mice. Within the population of 
      pDCs, the majority of the functional IDO-mediated suppressor activity segregated 
      with a novel subset of pDCs coexpressing the B-lineage marker CD19. We 
      hypothesize that IDO-mediated suppression by pDCs in TDLNs creates a local 
      microenvironment that is potently suppressive of host antitumor T cell responses.
FAU - Munn, David H
AU  - Munn DH
AD  - Department of Pediatrics, Institute for Molecular Medicine and Genetics, Medical 
      College of Georgia, Augusta, Georgia 30912, USA. dmunn@mail.mcg.edu.
FAU - Sharma, Madhav D
AU  - Sharma MD
FAU - Hou, Deyan
AU  - Hou D
FAU - Baban, Babak
AU  - Baban B
FAU - Lee, Jeffrey R
AU  - Lee JR
FAU - Antonia, Scott J
AU  - Antonia SJ
FAU - Messina, Jane L
AU  - Messina JL
FAU - Chandler, Phillip
AU  - Chandler P
FAU - Koni, Pandelakis A
AU  - Koni PA
FAU - Mellor, Andrew L
AU  - Mellor AL
LA  - eng
GR  - R01 CA096651/CA/NCI NIH HHS/United States
GR  - R01 HD041187/HD/NICHD NIH HHS/United States
GR  - R01 CA103220/CA/NCI NIH HHS/United States
GR  - R01 HD41187/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Antigens, CD19)
RN  - 0 (CD11c Antigen)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - EC 1.13.11.11 (Tryptophan Oxygenase)
SB  - IM
EIN - J Clin Invest. 2004 Aug;114(4):599
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigen-Presenting Cells/immunology/metabolism
MH  - Antigens, CD19/immunology
MH  - CD11c Antigen/immunology
MH  - Dendritic Cells/cytology/*enzymology/immunology
MH  - Female
MH  - Humans
MH  - *Immunosuppression Therapy
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase
MH  - Lymph Nodes/*immunology/pathology
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Neoplasms/*immunology/pathology
MH  - Random Allocation
MH  - Survival Rate
MH  - T-Lymphocytes/immunology
MH  - Tryptophan Oxygenase/genetics/*metabolism
PMC - PMC449750
EDAT- 2004/07/16 05:00
MHDA- 2004/09/01 05:00
PMCR- 2004/07/15
CRDT- 2004/07/16 05:00
PHST- 2004/03/15 00:00 [received]
PHST- 2004/05/25 00:00 [accepted]
PHST- 2004/07/16 05:00 [pubmed]
PHST- 2004/09/01 05:00 [medline]
PHST- 2004/07/16 05:00 [entrez]
PHST- 2004/07/15 00:00 [pmc-release]
AID - 21583 [pii]
AID - 10.1172/JCI21583 [doi]
PST - ppublish
SO  - J Clin Invest. 2004 Jul;114(2):280-90. doi: 10.1172/JCI21583.