Prevention of allogeneic fetal rejection by tryptophan catabolism.
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.
Munn
D H
DH
Program in Molecular Immunology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Zhou
M
M
Attwood
J T
JT
Bondarev
I
I
Conway
S J
SJ
Marshall
B
B
Brown
C
C
Mellor
A L
AL
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000276:immunology*; D005805:Genes, MHC Class I; D016654:Genes, RAG-1; D006183:H-2 Antigens / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019076:Transgenes; D014327:Trophoblasts / Q000201:enzymology*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C028129:tryptophan methyl ester; D016173:Macrophage Colony-Stimulating Factor; D014364:Tryptophan; D014366:Tryptophan Oxygenase