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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 30, 2008 Accepted September 19, 2008 Anti-CD3 preconditioning separates GVL from GVHD via modulating host dendritic and donor T cell migration in TBI-conditioned recipients Nainong Li, Ying Chen, Wei He, Tangsheng Yi, Dongchang Zhao, Chunyan Zhang, Chia-Lei Lin, Ivan Todorov, Fouad Kandeel, Stephen Forman, and Defu Zeng* Department of Hematology, Fujian Medical University Union Hospital, Fujian Institute of Hematology, China Division of Hematology & Hematopoietic Cell Transplantation, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States Department of Diabetes & Endocrinology, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States * Corresponding author; email: dzeng{at}coh.org. 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 hematological malignancies by allogeneic hematopoietic cell transplantation (HCT). Here, we show that preconditioning with anti-CD3 mAb before conditioning with total body irradiation prevents GVHD but retains GVL in a HCT model of MHC-mismatched C57BL/6 donor to BALB/c host. Prevention of GVHD is associated with inhibition of donor T expression of homing and chemokine receptors and inhibition of GVHD target tissue expression of chemokines. Furthermore, inhibition of donor T expression of gut homing 47 and chemokine receptor CCR9 by anti-CD3 preconditioning results from reduction of CD103+ DCs in draining mesenteric lymph nodes, which is associated with downregulation of DC expression of CCR7, a receptor required for tissue DC migration to draining LN. These results indicate that anti-CD3 preconditioning reduces not only tissue release of chemokines but also prevents tissue DC migration to draining LN and subsequently reduces draining LN DC's capacity in imprinting donor T 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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