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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3322-3330. Prepublished online as a Blood First Edition Paper on July 21, 2005; DOI 10.1182/blood-2005-05-1860. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-1860v1 106/9/3322    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 Terwey, T. H. Articles by van den Brink, M. R. M. Search for Related Content PubMed PubMed Citation Articles by Terwey, T. H. Articles by van den Brink, M. R. M. Related Collections Immunobiology Transplantation Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents TRANSPLANTATION CCR2 is required for CD8-induced graft-versus-host disease Theis H. Terwey, Theo D. Kim, Adam A. Kochman, Vanessa M. Hubbard, Sydney Lu, Johannes L. Zakrzewski, Teresa Ramirez-Montagut, Jeffrey M. Eng, Stephanie J. Muriglan, Glenn Heller, George F. Murphy, Chen Liu, Tulin Budak-Alpdogan, Onder Alpdogan, and Marcel R. M. van den Brink From the Department of Medicine and Immunology, and Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Pathology, Brigham and Women's Hospital, Boston, MA; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL; Department of Medicine, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ. Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Migration of donor-derived T cells into GVHD target organs plays a critical role in the development of GVHD and chemokines and their receptors are important molecules involved in this process. Here, we demonstrate in murine bone marrow transplantation models that the expression of the inflammatory CC chemokine receptor 2 (CCR2) on donor-derived CD8+ T cells is relevant for the control of CD8+ T-cell migration and development of GVHD. Recipients of CCR2-deficient (CCR2-/-) CD8+ T cells developed less damage of gut and liver than recipients of wild-type CD8+ T cells, which correlated with a reduction in overall GVHD morbidity and mortality. Assessment of donor CD8+ T-cell target organ infiltration revealed that CCR2-/- CD8+ T cells have an intrinsic migratory defect to the gut and liver. Other causes for the reduction in GVHD could be excluded, as alloreactive proliferation, activation, IFN- production and cytotoxicity of CCR2-/- CD8+ T cells were intact. Interestingly, the graft-versus-tumor effect mediated by CCR2-/- CD8+ T cells was preserved, which suggests that interference with T-cell migration by blockade of CCR2 signaling can separate GVHD from GVT activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Hori, Y. Naishiro, H. Sohma, N. Suzuki, N. Hatakeyama, M. Yamamoto, T. Sonoda, Y. Mizue, K. Imai, H. Tsutsumi, et al. CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease Blood, April 15, 2008; 111(8): 4403 - 4412. [Abstract] [Full Text] [PDF] T. D. Kim, T. H. Terwey, J. L. Zakrzewski, D. Suh, A. A. Kochman, M. E. Chen, C. G. King, C. Borsotti, J. Grubin, O. M. Smith, et al. Organ-derived dendritic cells have differential effects on alloreactive T cells Blood, March 1, 2008; 111(5): 2929 - 2940. [Abstract] [Full Text] [PDF] C. Borsotti, A. R. K. Franklin, S. X. Lu, T. D. Kim, O. M. Smith, D. Suh, C. G. King, A. Chow, C. Liu, O. Alpdogan, et al. Absence of donor T-cell-derived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity Blood, July 15, 2007; 110(2): 783 - 786. [Abstract] [Full Text] [PDF] M. R. McDevitt, D. Chattopadhyay, B. J. Kappel, J. S. Jaggi, S. R. Schiffman, C. Antczak, J. T. Njardarson, R. Brentjens, and D. A. Scheinberg Tumor Targeting with Antibody-Functionalized, Radiolabeled Carbon Nanotubes J. Nucl. Med., July 1, 2007; 48(7): 1180 - 1189. [Abstract] [Full Text] [PDF] C. Zhang, J. Lou, N. Li, I. Todorov, C.-L. Lin, Y.-A. Cao, C. H. Contag, F. Kandeel, S. Forman, and D. Zeng Donor CD8+ T Cells Mediate Graft-versus-Leukemia Activity without Clinical Signs of Graft-versus-Host Disease in Recipients Conditioned with Anti-CD3 Monoclonal Antibody J. Immunol., January 15, 2007; 178(2): 838 - 850. [Abstract] [Full Text] [PDF]

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