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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?
Author(s) -
Steckel N. K.,
Kuhn U.,
Beelen D. W.,
Elmaagacli A. H.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01212.x
Subject(s) - indoleamine 2,3 dioxygenase , medicine , immunology , transplantation , immune system , graft versus host disease , biology , tryptophan , biochemistry , amino acid
Indoleamine 2,3‐dioxygenase (IDO) is an interferon‐γ (IFN‐γ)‐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‐γ 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‐γ‐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‐γ‐induced IDO expression observed. These data suggest that IDO expression might be involved in the development of allogeneic immune tolerance.