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Blood, 15 May 2005, Vol. 105, No. 10, pp. 4127-4134. Prepublished online as a Blood First Edition Paper on January 27, 2005; DOI 10.1182/blood-2004-05-1726. This Article Full Text (PDF) All Versions of this Article: 2004-05-1726v1 105/10/4127    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 Hainz, U. Articles by Heitger, A. Search for Related Content PubMed PubMed Citation Articles by Hainz, U. Articles by Heitger, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 5, 2004 Accepted January 25, 2005 Monocyte-mediated T cell suppression and augmented monocyte tryptophan catabolism after human hematopoietic stem cell transplantation Ursula Hainz, Petra Obexer, Christiana Winkler, Peter Sedlmayr, Osamu Takikawa, Hildegard Greinix, Anita Lawitschka, Ulrike Potschger, Dietmar Fuchs, Stephan Ladisch, and Andreas Heitger* Children's Cancer Research Institute, St. Anna Children's Hospital, Vienna, Austria Tyrolean Cancer Research Institute, Innsbruck, Austria Institute of Medical Chemistry and Biochemistry, Innsbruck Medical University and Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria Institute of Histology and Embryology, Medical University of Graz, Graz, Austria Central Research Institute, Department of Pharmacology and Molecular Biochemistry, Hokkaido University, Sapporo, Japan Department of Medicine I, Vienna General Hospital, Vienna, Austria Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC, USA * Corresponding author; email: andreas.heitger{at}ccri.at. T-cell dysfunction after human hematopoietic stem cell transplantation (HSCT) is generally attributed to intrinsic T-cell defects. Here we show that the characteristic impaired proliferative responses to polyclonal stimulation of post-HSCT PBMC were markedly (four-fold) improved by T-cell enrichment. Conversely, addback of post-HSCT monocytes to these enriched T cells dampened their proliferative responses, suggesting that post-HSCT monocytes effectively mediate T-cell suppression. As a mechanism possibly contributing to monocyte-mediated T-cell suppression, we investigated monocyte tryptophan catabolism by indoleamine 2,3-dioxygenase into kynurenine, which has been implicated in regulating T-cell responses. Compared to controls, all post-HSCT monocyte-containing cell cultures (total PBMC, monocytes, and monocyte/T-cell co-cultures), but not monocyte-depleted populations, secreted elevated amounts of kynurenine. Blockade of tryptophan catabolism improved the proliferative responses. The slightly increased kynurenine release and substantial release of neopterin by unstimulated post-HSCT monocytes suggests that they were in a state of continuous activation. Superimposed on this state, stimulation of these cells caused a striking, additional increase (ten-fold) in kynurenine release, and they triggered marked apoptosis of autologous post-HSCT T-cells. We conclude that the amplified kynurenine release by post-HSCT monocytes, particularly induced upon stimulation, may underlie their suppressor activity that in turn may contribute to the depressed T-cell immune responses after HSCT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Jurgens, U. Hainz, D. Fuchs, T. Felzmann, and A. Heitger Interferon-{gamma}-triggered indoleamine 2,3-dioxygenase competence in human monocyte-derived dendritic cells induces regulatory activity in allogeneic T cells Blood, October 8, 2009; 114(15): 3235 - 3243. [Abstract] [Full Text] [PDF] C. Orabona, P. Puccetti, C. Vacca, S. Bicciato, A. Luchini, F. Fallarino, R. Bianchi, E. Velardi, K. Perruccio, A. Velardi, et al. Toward the identification of a tolerogenic signature in IDO-competent dendritic cells Blood, April 1, 2006; 107(7): 2846 - 2854. [Abstract] [Full Text] [PDF]

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