Document Detail

IDO inhibits T-cell function through suppressing Vav1 expression and activation.
MedLine Citation:
PMID:  19597340     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolic enzyme, plays an important role in immune escape through suppressing T-cell function. Since Vav1 signaling pathway regulates T cell homeostasis, this study was designed to test the hypothesis that IDO induces T-cell immunosuppression through inhibiting Vav1 signaling.
RESULTS: We found that IDO produced by IDO stably expressing CHO cells significantly inhibited interleukin (IL)-2 expression and proliferative response in T cells and increased apoptosis of T cells. IDO suppressed Vav1 mRNA and protein production in T cells. Furthermore, IDO inhibited TCR activation-induced Vav1 phosphorylation, which represents Vav1's activation state in T cells. These effects on T-cells induced by co-culture of CHO/IDO with T cells were attenuated by 1-MT.
MATERIALS AND METHODS: Chinese hamster ovary (CHO) cells were stably transfected with human IDO (CHO/IDO). CD3(+) T cells were isolated from human peripheral blood monouclear cells. After co-culture of CHO/IDO cells with T cells in the presence or absence of an anti-CD3 antibody to activate T cell receptor (TCR) and/or 1-methyl-L-tryptophan (1-MT) to inhibit IDO activity, T cell proliferation and apoptosis were determined. T cell total RNA and cellular protein samples were isolated for detecting Vav1 gene and protein expression and activation state.
CONCLUSIONS: The inhibitory effects of IDO on T cell immune responses may be through downregulation of Vav1 protein expression and activation. These studies provide insight into understanding the mechanisms of immune escape induced by IDO and therapeutic application of IDO inhibitors for cancer treatment.
Runmei Li; Feng Wei; Jinpu Yu; Hui Li; Xiubao Ren; Xishan Hao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-30
Journal Detail:
Title:  Cancer biology & therapy     Volume:  8     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-10-13     Completed Date:  2010-02-12     Revised Date:  2014-02-17    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1402-8     Citation Subset:  IM    
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MeSH Terms
CHO Cells
Cells, Cultured / cytology,  metabolism
Coculture Techniques
Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors,  genetics,  physiology*
Interleukin-2 / biosynthesis,  genetics
Lymphocyte Activation
Protein Processing, Post-Translational
Proto-Oncogene Proteins c-vav / antagonists & inhibitors*,  physiology
RNA, Messenger / biosynthesis,  genetics
Receptors, Antigen, T-Cell / immunology
Recombinant Fusion Proteins / physiology
T-Lymphocytes / cytology,  immunology*,  metabolism
Tryptophan / analogs & derivatives,  metabolism,  pharmacology
Tumor Escape / physiology
Reg. No./Substance:
0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 0/Interleukin-2; 0/Proto-Oncogene Proteins c-vav; 0/RNA, Messenger; 0/Receptors, Antigen, T-Cell; 0/Recombinant Fusion Proteins; 0/VAV1 protein, human; 8DUH1N11BX/Tryptophan
Comment In:
Cancer Biol Ther. 2009 Jul;8(14):1409-10   [PMID:  19502814 ]

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