Studying the immunosuppressive role of indoleamine 2,3‐dioxygenase: tryptophan metabolites suppress rat allogeneic T‐cell responses in vitro and in vivo

Summary Pregnancy is a natural model of successful tolerance induction against allogeneic tissues. Recent studies pointed to a role of indoleamine 2,3‐dioxygenase (IDO), a tryptophan‐degrading enzyme expressed in the placenta, in mediation of T‐cell suppression. We want to apply to organ transplanta...

Full description

Saved in:
Bibliographic Details
Published in:Transplant international 2005-01, Vol.18 (1), p.95-100
Main Authors: Bauer, Thomas M., Jiga, Lucian P., Chuang, Jing‐Jing, Randazzo, Marco, Opelz, Gerhard, Terness, Peter
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Dendritic Cells - drug effects
Dendritic Cells - immunology
General aspects
immunologic tolerance
immunosuppression
Immunosuppressive Agents - pharmacology
indoleamine 2,3‐dioxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase
kynurenine
Male
Medical sciences
Nephrology. Urinary tract diseases
Pharmacology. Drug treatments
Rats
Rats, Inbred Lew
Spleen - drug effects
Spleen - immunology
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Transplantation, Homologous - immunology
tryptophan
Tryptophan - metabolism
Tryptophan Oxygenase - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Pregnancy is a natural model of successful tolerance induction against allogeneic tissues. Recent studies pointed to a role of indoleamine 2,3‐dioxygenase (IDO), a tryptophan‐degrading enzyme expressed in the placenta, in mediation of T‐cell suppression. We want to apply to organ transplantation what nature has developed for suppression of fetal rejection during pregnancy. Here we analyze whether IDO‐induced tryptophan metabolites are able to suppress the allogeneic T‐cell response and allograft rejection in rats. Rat lymphocytes were stimulated with allogeneic dendritic cells in vitro in the presence of increasing amounts of tryptophan metabolites (kynurenine, 3‐hydroxykynurenine, anthranilic acid, 3‐hydroxyanthranilic acid and quinolinic acid) and T‐cell proliferation was determined. The findings showed that kynurenine, 3‐hydroxykynurenine and 3‐hydroxyanthranilic acid strongly suppress the T‐cell response, whereas anthranilic and quinolinic acid are noneffective. Vital staining of cells with subsequent fluorescence‐activated cell sorter analyses demonstrated that suppression is mediated by T‐cell death. Thereafter, the action of metabolites was analyzed in a skin allograft model (BN→LEW). Lewis recipients received daily s.c. injections of tryptophan metabolite mixture (kynurenine + 3‐hydroxyanthranilic acid), cyclosporin A (positive control), or no treatment (negative control). The metabolites induced a significant prolongation (P = 0.0018) of graft survival. We conclude that IDO‐induced tryptophan metabolites suppress the T‐cell response and prolong allograft survival in rats.
ISSN:0934-0874
1432-2277
DOI:10.1111/j.1432-2277.2004.00031.x