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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 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 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 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. Related Collections Immunobiology Phagocytes Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 October 2003, Vol. 102, No. 7, pp. 2522-2531 IMMUNOBIOLOGY 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 From the Jordan Laboratory for Hemato-Oncology, Dept of Hematology, University Medical Center Utrecht, the Netherlands. The safe application of new strategies for the treatment of graft-versus-host disease (GVHD) 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 (huPBMCs) into NOD-SCID (nonobese diabetic-severe combined immunodeficient)/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 huPBMCs into RAG2-/- c-/-mice. Our results show a high human T-cell chimerism of more than 20% (up to 98%) in more than 90% of mice, associated with a consistent development of XGVHD within 14 to 28 days and a total mortality rate of 85% shorter than 2 months. After murine macrophage depletion, engraftment was earlier and equally high with lower doses of huPBMCs. 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. One of 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 huPBMCs in RAG2-/- c-/- mice. Murine and human macrophages do not seem to be necessary for acute X-GVHD in this model. (Blood. 2003;102:2522-2531) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Rozemuller, E. van der Spek, L. H. Bogers-Boer, M. C. Zwart, V. Verweij, M. Emmelot, R. W. Groen, R. Spaapen, A. C. Bloem, H. M. Lokhorst, et al. A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect Haematologica, July 1, 2008; 93(7): 1049 - 1057. [Abstract] [Full Text] [PDF] E. Zorn and J. Ritz Studying Human Regulatory T Cells In vivo. Clin. Cancer Res., September 15, 2006; 12(18): 5265 - 5267. [Full Text] [PDF] T. Mutis, R. S. van Rijn, E. R. 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Verdonck, A. C.M. Martens, et al. Induction of Xenogeneic Graft-Versus-Host Disease through Administration of HuPBMC to Immune Deficient RAG2-/-{gamma}c-/- Mice: A Model for B Cell-Involvement in Chronic Graft-Versus-Host Disease. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 3099 - 3099. [Abstract] S. Roychowdhury, B. W. Blaser, A. G. Freud, K. Katz, D. Bhatt, A. K. Ferketich, V. Bergdall, D. Kusewitt, R. A. Baiocchi, and M. A. Caligiuri IL-15 but not IL-2 rapidly induces lethal xenogeneic graft-versus-host disease Blood, October 1, 2005; 106(7): 2433 - 2435. [Abstract] [Full Text] [PDF] R. Gimeno, K. Weijer, A. Voordouw, C. H. Uittenbogaart, N. Legrand, N. L. Alves, E. Wijnands, B. Blom, and H. Spits Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- {gamma}c-/- mice: functional inactivation of p53 in developing T cells Blood, December 15, 2004; 104(13): 3886 - 3893. [Abstract] [Full Text] [PDF] T. Mutis, R. S. van Rijn, E. R. Simonetti, T. Aarts, M. Emmelot, and S. B. Ebeling Human CD4+ CD25+ Regulatory T Cells Effectively Control Xenogeneic-GvHD Induced by Autologous T Cells in Rag2-/- {gamma}c-/- Immune-Deficient Mice. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 301 - 301. [Abstract]

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