PMID- 19234174
OWN - NLM
STAT- MEDLINE
DCOM- 20090421
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 182
IP  - 5
DP  - 2009 Mar 1
TI  - Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma 
      cells and prime the differentiation of CD4+CD25+Foxp3+ regulatory T cells.
PG  - 2795-807
LID - 10.4049/jimmunol.0712671 [doi]
AB  - Dendritic cells (DCs) have a central role in the development of adaptive immune 
      responses, including antitumor immunity. Factors present in the tumor milieu can 
      alter the maturation of DCs and inhibit their capacity to activate T cells. Using 
      gene expression analysis, we found that human DCs increased the expression of 
      TGF-beta1 transcripts following culture with human lung carcinoma cells (LCCs). 
      These DCs produced increased amounts of TGF-beta1 protein compared with DCs not 
      exposed to tumor cells. LCCs also decreased the expression of CD86 and HLA-DR by 
      immature DCs. Furthermore, LCCs decreased CD86 expression and the production of 
      TNF-alpha and IL-12 p70 by mature DCs. Moreover, LCCs also converted mature DCs 
      into cells producing TGF-beta1. These TGF-beta1-producing DCs were poor at 
      eliciting the activation of naive CD4(+) T cells and sustaining their 
      proliferation and differentiation into Th1 (IFN-gamma(+)) effectors. Instead, 
      TGF-beta1-producing DCs demonstrated an increased ability to generate 
      CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress the proliferation of T 
      lymphocytes. These results identify a novel mechanism by which the function of 
      human DCs is altered by tumor cells and contributes to the evasion of the immune 
      response.
FAU - Dumitriu, Ingrid E
AU  - Dumitriu IE
AD  - Centre for Inflammation Research, Queen's Medical Research Institute, University 
      of Edinburgh, Edinburgh, United Kingdom. i.dumitriu@sgul.ac.uk
FAU - Dunbar, Donald R
AU  - Dunbar DR
FAU - Howie, Sarah E
AU  - Howie SE
FAU - Sethi, Tariq
AU  - Sethi T
FAU - Gregory, Christopher D
AU  - Gregory CD
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (B7-2 Antigen)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - B7-2 Antigen/biosynthesis/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/*immunology/metabolism
MH  - Cell Differentiation/*immunology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*immunology/metabolism/pathology
MH  - Down-Regulation/immunology
MH  - Forkhead Transcription Factors/*biosynthesis
MH  - HLA-DR Antigens/biosynthesis/metabolism
MH  - Humans
MH  - Interleukin-12/antagonists & inhibitors/biosynthesis
MH  - Interleukin-2 Receptor alpha Subunit/*biosynthesis
MH  - Lung Neoplasms/*immunology/metabolism
MH  - Lymphocyte Activation/immunology
MH  - Monocytes/immunology/metabolism
MH  - T-Lymphocytes, Regulatory/cytology/*immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/biosynthesis
EDAT- 2009/02/24 09:00
MHDA- 2009/04/22 09:00
CRDT- 2009/02/24 09:00
PHST- 2009/02/24 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2009/04/22 09:00 [medline]
AID - 182/5/2795 [pii]
AID - 10.4049/jimmunol.0712671 [doi]
PST - ppublish
SO  - J Immunol. 2009 Mar 1;182(5):2795-807. doi: 10.4049/jimmunol.0712671.