Indoleamine 2,3-dioxygenase expression in patients with acute graft-versus-host disease after allogeneic stem cell transplantation and in pregnant women: association with the induction of allogeneic immune tolerance?
Indoleamine 2,3-dioxygenase (IDO) is an interferon-gamma (IFN-gamma)-induced enzyme, which is suggested to play an important role in the prevention of allogeneic fetal rejection. IDO effects the suppression of T-cell activity by catabolizing the essential amino acid l-tryptophan. We studied IDO expression by reverse transcription polymerase chain reaction (RT-PCR) in dendritic cells and by real-time RT-PCR in monocytes of patients undergoing allogeneic transplantation for leukaemia, who developed acute graft-versus-host disease (aGvHD), and compared the IDO expression with that of pregnant women and healthy volunteers. A spontaneous IDO expression was detected in the monocytes of 20 pregnant women with an IDO/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratio at a median of 1.0%, whereas none of 15 healthy volunteers or patients after allogeneic transplant had any detectable spontaneous IDO expression. The IDO expression increased by in vitro IFN-gamma stimulation in pregnant women (median 116%), healthy volunteers (median 11.7%) and patients with a low-grade aGvHD (grades 0-II) 28 days after transplant (median 433%) but not in patients with a severe aGvHD (grades III-IV) (median 0%), which was highly significant (P < 0.01). IDO expression was also measured in dendritic cells by qualitative RT-PCR, where a spontaneous IDO expression was detected in 16 of 31 (52%) pregnant women versus none of 17 healthy volunteers and none of 62 studied patients after transplant. IFN-gamma-induced IDO expression was detected in all pregnant women, all volunteers and 47 of 49 (96%) patients with a low-grade aGvHD (grades 0-II) after transplant, whereas only in two of 13 (16%) patients with aGvHD grade III-IV was IFN-gamma-induced IDO expression observed. These data suggest that IDO expression might be involved in the development of allogeneic immune tolerance.
Steckel
N K
NK
Department of Bone Marrow Transplantation; and Department of Gynecology, University Hospital of Essen, Essen, Germany. nina.steckel@uni-essen.de
Kuhn
U
U
Beelen
D W
DW
Elmaagacli
A H
AH
D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000276:immunology; D011247:Pregnancy / Q000276:immunology / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014366:Tryptophan Oxygenase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012313:RNA; D014366:Tryptophan Oxygenase