Prevention of Allogeneic Fetal Rejection by Tryptophan Catabolism
David H. Munn,
Min Zhou,
John T. Attwood,
Igor Bondarev,
Simon J. Conway,
Brendan Marshall,
Corrie Brown,
Andrew L. Mellor
*
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.
D. H. Munn, M. Zhou, J. T. Attwood, I. Bondarev, S. J. Conway, B. Marshall, A. L. Mellor, Programs in Molecular
Immunology and Developmental Biology, Institute of Molecular Medicine
and Genetics, and Department of Pediatrics, Medical College of Georgia
(MCG), 1120 15th Street, Augusta, GA 30912, USA. C. Brown, Department
of Pathology, University of Georgia, Athens, GA 30602, USA.
*
To whom correspondence should be addressed. E-mail:
mellor{at}immag.mcg.edu
