Prevention of Allogeneic Fetal Rejection by Tryptophan Catabolism

• DOI: 10.1126/science.281.5380.1191
• Publication Date: 2002-07-27T09:43:20Z
• Authors: David H. Munn; Min Zhou; John T. Attwood; Igor Bondarev; Simon J. Conway; Brendan Marshall; Corrie Brown; Andrew L. Mellor
• Keywords: Male; 0301 basic medicine; Genes, RAG-1; Macrophage Colony-Stimulating Factor; Placenta; T-Lymphocytes; H-2 Antigens; Genes, MHC Class I; Trophoblasts; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Fetus; Pregnancy; Immune Tolerance; Mice, Inbred CBA; Animals; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Female; Transgenes; Enzyme Inhibitors

In 1953 Medawar pointed out that survival of the genetically disparate (allogeneic) mammalian conceptus contradicts the laws of tissue transplantation. Rapid T cell–induced rejection of all allogeneic concepti occurred when pregnant mice were treated with a pharmacologic inhibitor of indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme expressed by trophoblasts and macrophages. Thus, by catabolizing tryptophan, the mammalian conceptus suppresses T cell activity and defends itself against rejection.