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Blood, 22 January 2009, Vol. 113, No. 4, pp. 953-962. Prepublished online as a Blood First Edition Paper on October 15, 2008; DOI 10.1182/blood-2008-06-165522. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-165522v1 113/4/953    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 Li, N. Articles by Zeng, D. Search for Related Content PubMed PubMed Citation Articles by Li, N. Articles by Zeng, D. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Anti-CD3 preconditioning separates GVL from GVHD via modulating host dendritic cell and donor T-cell migration in recipients conditioned with TBI Nainong Li13,*, Ying Chen1,2,*, Wei He1,2, Tangsheng Yi1,2, Dongchang Zhao1,2, Chunyan Zhang1,2, Chia-Lei Lin1,2, Ivan Todorov1, Fouad Kandeel1, Stephen Forman2, and Defu Zeng1,2 1 Department of Diabetes and Endocrinology and 2 Department of Hematology and Hematopoietic Cell Transplantation, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA; and 3 Department of Hematology, Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fuzhou, China Host dendritic cells (DCs) play a critical role in initiating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL), and separation of GVL from GVHD remains a major challenge in the treatment of hematologic malignancies by allogeneic hematopoietic cell transplantation (HCT). Here, we show that preconditioning with anti-CD3 monoclonal antibody before conditioning with total body irradiation (TBI) prevents GVHD but retains GVL in a HCT model of major histocompatibility complex (MHC)–mismatched C57BL/6 donor to BALB/c host. Prevention of GVHD is associated with inhibition of donor T-cell expression of homing and chemokine receptors, and inhibition of GVHD target tissue expression of chemokines. Furthermore, inhibition of donor T-cell expression of gut homing 4β7 and chemokine receptor (CCR)9 by anti-CD3 preconditioning results from a reduction of CD103+ DCs in draining mesenteric lymph nodes (LNs), which is associated with down-regulation of DC expression of CCR7, a receptor required for tissue DC migration to draining LNs. These results indicate that anti-CD3 preconditioning reduces not only tissue release of chemokines but also prevents tissue DC migration to draining LNs and subsequently reduces the capacity of DCs of draining LNs to imprint donor T-cell tissue tropism. Therefore, modulation of host DCs by anti-CD3 preconditioning before HCT represents a new approach for separating GVL from GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Yi, Y. Chen, L. Wang, G. Du, D. Huang, D. Zhao, H. Johnston, J. Young, I. Todorov, D. T. Umetsu, et al. Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease Blood, October 1, 2009; 114(14): 3101 - 3112. [Abstract] [Full Text] [PDF]

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