SEARCH:   Advanced

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 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 Citation Map 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. Related Collections Immunobiology Phagocytes Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION 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 Pütschger, Dietmar Fuchs, Stephan Ladisch, and Andreas Heitger From the Children's Cancer Research Institute, St Anna Children's Hospital, and the Vienna General Hospital, Department of Medicine I, Vienna, Austria; the Tyrolean Cancer Research Institute, Innsbruck, Austria; the Institute of Medical Chemistry and Biochemistry, Innsbruck Medical University and Ludwig Boltzmann Institute of AIDS-Research, Austria; the Institute of Histology and Embryology, Medical University of Graz, Austria; the Central Research Institute, Department of Pharmacology and Molecular Biochemistry, Hokkaido University, Sapporo, Japan; and the Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC. 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 peripheral blood mononuclear cells (PB-MCs) were markedly (4-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 with controls, all post-HSCT monocyte-containing cell cultures (total PBMCs, monocytes, and monocyte/T-cell cocultures), 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 (10-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, which 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: M. Magatti, S. De Munari, E. Vertua, L. Gibelli, G. S. Wengler, and O. Parolini Human Amnion Mesenchyme Harbors Cells with Allogeneic T-Cell Suppression and Stimulation Capabilities Stem Cells, January 1, 2008; 26(1): 182 - 192. [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]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020