title: Tryptophan catabolism and T cell responses.
abstract: Cells expressing indoleamine 2,3 dioxygenase (IDO) play key roles in regulating adaptive immune responses orchestrated by T cells. In this report we discuss our working model, the tryptophan depletion hypothesis, to explain links between IDO expression and inhibition of T cell responses. We posit that IDO+ cells, particularly professional antigen presenting cells (APCs) promote T cell entry but block cell cycle progression due to tryptophan catabolism. We discuss experimental evidence supporting predictions from the tryptophan depletion hypothesis and the implications that this model has for understanding the origin of tolerant states that explain immunological paradoxes, such as fetal survival, tumor persistence and failure to eradicate pathogens like HIV that cause persistent infections.
authors.affiliation: Program in Molecular Immunology, Institute of Molecular Medicine and Genetics, Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA. amellor@mail.mcg.edu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mellor
authors.forename: David
authors.initials: D
authors.lastname: Munn
authors.forename: Phillip
authors.initials: P
authors.lastname: Chandler
authors.forename: Derin
authors.initials: D
authors.lastname: Keskin
authors.forename: Theodore
authors.initials: T
authors.lastname: Johnson
authors.forename: Brendan
authors.initials: B
authors.lastname: Marshall
authors.forename: Kanchan
authors.initials: K
authors.lastname: Jhaver
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007249:Inflammation / Q000209:etiology; D008213:Lymphocyte Activation; D018448:Models, Immunological; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan; D014366:Tryptophan Oxygenase