Tryptophan catabolism and T cell responses.
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.
Mellor
Andrew L
AL
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
Munn
David
D
Chandler
Phillip
P
Keskin
Derin
D
Johnson
Theodore
T
Marshall
Brendan
B
Jhaver
Kanchan
K
Baban
Babak
B
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
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan; D014366:Tryptophan Oxygenase