Tryptophan catabolism prevents maternal T cells from activating lethal anti-fetal immune responses.
The murine conceptus is protected from maternal immunity by cells expressing indoleamine dioxygenase (IDO), which catabolizes tryptophan. Induction of lethal maternal anti-fetal immunity requires effective pharmacologic inhibition of IDO enzyme activity and the presence of maternal T cells, but not B cells and also depends on the degree of maternal-fetal tissue incompatibility. Based on these findings, we propose a model to explain the role of IDO in suppressing maternal immunity and the mechanism of fetal allograft rejection, when IDO activity is inhibited during gestation. This model incorporates observations that fetal allograft rejection is T cell dependent, antibody-independent and is accompanied by a novel type of inflammation involving extensive complement deposition at the maternal-fetal interface, when IDO activity is blocked during murine pregnancy.
Mellor
A L
AL
Department of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, CA 2006, Augusta, GA 30912-2000, USA. mellor@immag.mcg.edu
Munn
D H
DH
D000818:Animals; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008431:Maternal-Fetal Exchange / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D011256:Pregnancy Outcome; D013601:T-Lymphocytes / Q000276:immunology*; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors / Q000502:physiology
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan; D003165:Complement System Proteins; D014366:Tryptophan Oxygenase