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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4619-4621.
Prepublished online as a Blood First Edition Paper on March 4, 2004; DOI 10.1182/blood-2003-11-3909.
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IMMUNOBIOLOGY Brief report
Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenasemediated tryptophan degradation
Roland Meisel,
Andree Zibert,
Maurice Laryea,
Ulrich Göbel,
Walter Däubener, and
Dagmar Dilloo
From the Clinic of Pediatric Oncology, Hematology and Immunology, University Hospital, Düsseldorf, Germany; Clinic of General Pediatrics, University Hospital, Düsseldorf, Germany; and Institute of Medical Microbiology, University Hospital, Düsseldorf, Germany.
Marrow stromal cells (MSCs) inhibit allogeneic T-cell responses, yet the molecular mechanism mediating this immunosuppressive effect of MSCs remains controversial. Recently, expression of indoleamine 2,3-dioxygenase (IDO), which is induced by interferon- (IFN- ) and catalyzes the conversion from tryptophan to kynurenine, has been identified as a T-cell inhibitory effector pathway in professional antigen-presenting cells. Here we show that human MSCs express IDO protein and exhibit functional IDO activity upon stimulation with IFN- . MSCs inhibit allogeneic T-cell responses in mixed lymphocyte reactions (MLRs). Concomitantly, IDO activity resulting in tryptophan depletion and kynurenine production is detected in MSC/MLR coculture supernatants. Addition of tryptophan significantly restores allogeneic T-cell proliferation, thus identifying IDO-mediated tryptophan catabolism as a novel T-cell inhibitory effector mechanism in human MSCs. As IDO-mediated T-cell inhibition depends on MSC activation, modulation of IDO activity might alter the immunosuppressive properties of MSCs in different therapeutic applications. (Blood. 2004;103:4619-4621)

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