T cell apoptosis by tryptophan catabolism

✍ Scribed by Fallarino, F; Grohmann, U; Vacca, C; Bianchi, R; Orabona, C; Spreca, A; Fioretti, M C; Puccetti, P

• Book ID: 110016405
• Publisher: Nature Publishing Group
• Year: 2002
• Tongue: English
• Weight: 280 KB
• Volume: 9
• Category: Article
• ISSN: 1350-9047
• DOI: 10.1038/sj.cdd.4401073

✦ Synopsis

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that, expressed by different cell types, has regulatory effects on T cells resulting from tryptophan depletion in specific local tissue microenvironments. Different mechanisms, however, might contribute to IDO-dependent immune regulation. We show here that tryptophan metabolites in the kynurenine pathway, such as 3-hydroxyanthranilic and quinolinic acids, will induce the selective apoptosis in vitro of murine thymocytes and of Th1 but not Th2 cells. T cell apoptosis was observed at relatively low concentrations of kynurenines, did not require Fas/Fas ligand interactions, and was associated with the activation of caspase-8 and the release of cytochrome c from mitochondria. When administered in vivo, the two kynurenines caused depletion of specific thymocyte subsets in a fashion qualitatively similar to dexamethasone. These data suggest that the selective deletion of T lymphocytes may be a major mechanism whereby tryptophan metabolism affects immunity under physiopathologic conditions.