Tryptophan catabolism by indoleamine 2,3-dioxygenase (IDO) induces apoptosis in T cells, particularly Th1 cells, through the kynurenine pathway. This study shows that tryptophan metabolites such as 3-hydroxyanthranilic acid (3-HAA) and quinolinic acid (QUIN) cause selective apoptosis of murine thymocytes and Th1 cells in vitro. Apoptosis occurs at low concentrations of kynurenines and does not require Fas/Fas ligand interactions, but is associated with caspase-8 activation and cytochrome c release from mitochondria. In vivo, these kynurenines cause thymocyte subset depletion similar to dexamethasone. These findings suggest that tryptophan metabolism may regulate T cell homeostasis and self-tolerance, and contribute to disease states through imbalances in T helper responses. The study also highlights the role of IDO-expressing dendritic cells in mediating T cell apoptosis, and the potential of tryptophan metabolites in immunoregulation. The results indicate that tryptophan catabolism may have significant biological implications in immune regulation and disease.Tryptophan catabolism by indoleamine 2,3-dioxygenase (IDO) induces apoptosis in T cells, particularly Th1 cells, through the kynurenine pathway. This study shows that tryptophan metabolites such as 3-hydroxyanthranilic acid (3-HAA) and quinolinic acid (QUIN) cause selective apoptosis of murine thymocytes and Th1 cells in vitro. Apoptosis occurs at low concentrations of kynurenines and does not require Fas/Fas ligand interactions, but is associated with caspase-8 activation and cytochrome c release from mitochondria. In vivo, these kynurenines cause thymocyte subset depletion similar to dexamethasone. These findings suggest that tryptophan metabolism may regulate T cell homeostasis and self-tolerance, and contribute to disease states through imbalances in T helper responses. The study also highlights the role of IDO-expressing dendritic cells in mediating T cell apoptosis, and the potential of tryptophan metabolites in immunoregulation. The results indicate that tryptophan catabolism may have significant biological implications in immune regulation and disease.