The study investigates the mechanism by which dendritic cells (DCs) expressing indoleamine 2,3-dioxygenase (IDO) suppress allogeneic T cell proliferation. IDO is an enzyme that degrades tryptophan, an essential amino acid for cell proliferation. The researchers inserted the human IDO gene into an adenoviral vector and expressed it in DCs, which then decreased tryptophan levels and increased kynurenine, a major tryptophan metabolite. This suppression of allogeneic T cell proliferation was mediated by kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid, which acted additively. The suppressive effects were time-dependent and preferentially affected activated T cells, as well as B and natural killer (NK) cells, while DCs remained unaffected. These findings provide insights into the suppressive mechanisms mediated by DCs and explain biological processes where IDO activity is increased, such as fetal protection during pregnancy and T cell death in HIV-infected patients.The study investigates the mechanism by which dendritic cells (DCs) expressing indoleamine 2,3-dioxygenase (IDO) suppress allogeneic T cell proliferation. IDO is an enzyme that degrades tryptophan, an essential amino acid for cell proliferation. The researchers inserted the human IDO gene into an adenoviral vector and expressed it in DCs, which then decreased tryptophan levels and increased kynurenine, a major tryptophan metabolite. This suppression of allogeneic T cell proliferation was mediated by kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid, which acted additively. The suppressive effects were time-dependent and preferentially affected activated T cells, as well as B and natural killer (NK) cells, while DCs remained unaffected. These findings provide insights into the suppressive mechanisms mediated by DCs and explain biological processes where IDO activity is increased, such as fetal protection during pregnancy and T cell death in HIV-infected patients.