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Inhibition of indoleamine 2,3-dioxygenase in mixed lymphocyte reaction affects glucose influx and enzymes involved in aerobic glycolysis and glutaminolysis in alloreactive T-cells.
- Source :
-
Human immunology [Hum Immunol] 2013 Dec; Vol. 74 (12), pp. 1501-9. Date of Electronic Publication: 2013 Aug 28. - Publication Year :
- 2013
-
Abstract
- Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity. T-cell proliferation and differentiation to effector cells require increased glucose consumption, aerobic glycolysis and glutaminolysis. The effect of IDO on the above metabolic pathways was evaluated in alloreactive T-cells. Mixed lymphocyte reaction (MLR) in the presence or not of the IDO inhibitor, 1-methyl-dl-tryptophan (1-MT), was used. In MLRs, 1-MT decreased tryptophan consumption, increased cell proliferation, glucose influx and lactate production, whereas it decreased tricarboxylic acid cycle activity. In T-cells, from the two pathways that could sense tryptophan depletion, i.e. general control nonrepressed 2 (GCN2) kinase and mammalian target of rapamycin complex 1, 1-MT reduced only the activity of the GCN2 kinase. Additionally 1-MT treatment of MLRs altered the expression and/or the phosphorylation state of glucose transporter-1 and of key enzymes involved in glucose metabolism and glutaminolysis in alloreactive T-cells in a way that favors glucose influx, aerobic glycolysis and glutaminolysis. Thus in alloreactive T-cells, IDO through activation of the GCN2 kinase, decreases glucose influx and alters key enzymes involved in metabolism, decreasing aerobic glycolysis and glutaminolysis. Acting in such a way, IDO could be considered as a constraining factor for alloreactive T-cell proliferation and differentiation to effector T-cell subtypes.<br /> (Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Citric Acid Cycle drug effects
Enzyme Activation drug effects
Glucose Transporter Type 1 genetics
Glucose Transporter Type 1 metabolism
Glycolysis
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Lymphocyte Culture Test, Mixed
Male
Mechanistic Target of Rapamycin Complex 1
Multiprotein Complexes metabolism
Protein Serine-Threonine Kinases metabolism
T-Lymphocyte Subsets drug effects
TOR Serine-Threonine Kinases metabolism
Tryptophan analogs & derivatives
Tryptophan metabolism
Tryptophan pharmacology
Glucose metabolism
Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1166
- Volume :
- 74
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Human immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23993986
- Full Text :
- https://doi.org/10.1016/j.humimm.2013.08.268