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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2002-10-3241. This Article Full Text (PDF) All Versions of this Article: 2002-10-3241v1 102/7/2522    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 van Rijn, R. S Articles by Ebeling, S. B Search for Related Content PubMed PubMed Citation Articles by van Rijn, R. S Articles by Ebeling, S. B Social Bookmarking                   What's this? Submitted October 25, 2002 Accepted May 27, 2003 A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/-c-/- double mutant mice Rozemarijn S van Rijn, Elles R Simonetti, Anton Hagenbeek, Marieke C H Hogenes, Roel A de Weger, Marijke R Canninga-van Dijk, Kees Weijer, Hergen Spits, Gert Storm, Louis van Bloois, Ger Rijkers, Anton C M Martens, and Saskia B Ebeling* Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands Department of Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, The Netherlands * Corresponding author; email: s.ebeling{at}azu.nl. The safe application of new strategies for the treatment of graft-versus-host disease is hampered by the lack of a clinically relevant model for preclinical testing. Current models are based on intraperitoneal transfer of human peripheral blood mononuclear cells (huPBMC) into (NOD-)SCID mice. Intravenous transfer would be preferred, but this has always been ineffective. We developed a new model for xenogeneic GVHD (X-GVHD) by intravenous transfer of huPBMC into RAG2-/-c-/- mice. Our results show a high human T cell chimerism of >20% (up to 98%) in >90% of mice, associated with a consistent development of X-GVHD within 14-28 days and a total mortality rate of 85% <2 months. After murine macrophage depletion, engraftment was earlier and equally high with lower doses of huPBMC. Human macrophages were also absent in these mice. Purified huCD3+ cells showed a similar X-GVH effect, with contribution of both CD4 and CD8 phenotypes. Human immunoglobulins and cytokines were produced in diseased mice. 1/30 mice developed chronic X-GVHD with skin histology similar to human GVHD. In conclusion, we present a new model for X-GVHD by intravenous transfer of huPBMC in RAG2-/-c-/- mice. Murine and human macrophages do not seem to be necessary for acute X-GVHD in this model. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Bohana-Kashtan, S. Morisot, R. Hildreth, C. Brayton, H. I. Levitsky, and C. I. Civin Selective Reduction of Graft-versus-Host Disease-Mediating Human T Cells by Ex Vivo Treatment with Soluble Fas Ligand J. Immunol., July 1, 2009; 183(1): 696 - 705. [Abstract] [Full Text] [PDF] J. Wilson, H. Cullup, R. Lourie, Y. Sheng, A. Palkova, K. J. Radford, A. M. Dickinson, A. M. Rice, D. N.J. Hart, and D. J. Munster Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease J. Exp. 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[Full Text] [PDF] T. Mutis, R. S. van Rijn, E. R. Simonetti, T. Aarts-Riemens, M. E. Emmelot, L. van Bloois, A. Martens, L. F. Verdonck, and S. B. Ebeling Human Regulatory T Cells Control Xenogeneic Graft-versus-Host Disease Induced by Autologous T Cells in RAG2-/-{gamma}c-/- Immunodeficient Mice. Clin. Cancer Res., September 15, 2006; 12(18): 5520 - 5525. [Abstract] [Full Text] [PDF] A. Bondanza, V. Valtolina, Z. Magnani, M. Ponzoni, K. Fleischhauer, M. Bonyhadi, C. Traversari, F. Sanvito, S. Toma, M. Radrizzani, et al. Suicide gene therapy of graft-versus-host disease induced by central memory human T lymphocytes Blood, March 1, 2006; 107(5): 1828 - 1836. [Abstract] [Full Text] [PDF] N. Legrand, K. Weijer, and H. Spits Experimental Models to Study Development and Function of the Human Immune System In Vivo J. Immunol., February 15, 2006; 176(4): 2053 - 2058. [Abstract] [Full Text] [PDF] M. C. Canninga-van Dijk, R. S. van Rijn, E. R. Simonetti, M. C. Hogenes, S. Smulders, R. 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