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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. This Article Full Text (PDF) All Versions of this Article: 2003-11-3909v1 103/12/4619    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Meisel, R. Articles by Dilloo, D. Search for Related Content PubMed PubMed Citation Articles by Meisel, R. Articles by Dilloo, D. Social Bookmarking                   What's this? Submitted November 18, 2003 Accepted February 24, 2004 Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase mediated tryptophan degradation Roland Meisel, Andree Zibert, Maurice Laryea, Ulrich Gobel, Walter Daubener, and Dagmar Dilloo* Clinic of Pediatric Oncology, Hematology and Immunology, University Hospital, Duesseldorf, Germany Clinic of General Pediatrics, University Hospital, Duesseldorf, Germany Institute of Medical Microbiology, University Hospital, Duesseldorf, Germany * Corresponding author; email: dilloo{at}uni-duesseldorf.de. 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 co-culture 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. 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