Prevention of allogeneic fetal rejection by tryptophan catabolism

Science. 1998 Aug 21;281(5380):1191-3. doi: 10.1126/science.281.5380.1191.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology
  • Female
  • Fetus / immunology*
  • Genes, MHC Class I
  • Genes, RAG-1
  • H-2 Antigens / genetics
  • Humans
  • Immune Tolerance*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Macrophage Colony-Stimulating Factor / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Placenta / enzymology
  • Pregnancy
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transgenes
  • Trophoblasts / enzymology*
  • Tryptophan / analogs & derivatives
  • Tryptophan / metabolism*
  • Tryptophan / pharmacology
  • Tryptophan Oxygenase / antagonists & inhibitors
  • Tryptophan Oxygenase / metabolism*

Substances

  • Enzyme Inhibitors
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • tryptophan methyl ester
  • Macrophage Colony-Stimulating Factor
  • Tryptophan
  • Tryptophan Oxygenase