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Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2002-01-0023. This Article Full Text (PDF) All Versions of this Article: 2002-01-0023v1 100/5/1903    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 Mapara, M. Y Articles by Sykes, M. Search for Related Content PubMed PubMed Citation Articles by Mapara, M. Y Articles by Sykes, M. Social Bookmarking                   What's this? Submitted January 8, 2002 Accepted April 29, 2002 Donor lymphocyte infusions (DLI) mediate superior graft-versus-leukemia (GvL) effects in mixed compared to fully allogeneic chimeras: A critical role for host antigen-presenting cells Markus Y Mapara, Yong-Mi Kim, Sheng-Ping Wang, Roderick Bronson, David H Sachs, and Megan Sykes* Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Boston, MA, USA School of Veterinary Medicine, Tufts University, North Grafton, MA, USA * Corresponding author; email: megan.sykes{at}tbrc.mgh.harvard.edu. In mice, donor leukocyte infusions (DLI) given to established mixed allogeneic chimeras can mediate powerful graft-vs.-host reactions confined to the lymphohematopoietic system without inducing graft-vs.-host-disease (GVHD). In a clinical trial attempting to capture this approach to achieve graft-vs.leukemia/lymphoma (GVL) effects without GVHD, we have observed surprisingly powerful anti-tumor effects of DLI in patients achieving mixed chimerism after non-myeloablative bone marrow transplantation. This observation led us to hypothesize that host antigen-presenting cells in mixed chimeras might be required to optimally present recipient antigens to the donor lymphocytes, leading to maximal graft-versus-tumor effects. To test this hypothesis, we established mixed and fully allogeneic hematopoietic chimeras in B6 mice and evaluated the effect of DLI on EL4 T-cell lymphoma. DLI administration to mixed chimeras produced dramatically improved leukemia-free survival compared to administration of DLI to full donor chimeras. DLI also converted mixed chimeras to full chimeras without causing GVHD. The magnitude of the GVL effect was dependent on the level of MHC class I expression on recipient hematopoietic cells in mixed chimeras. Thus, induction of mixed chimerism followed by delayed DLI provides an approach to inhibiting GVHD that optimizes GVL effects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Kamiryo, M. Eto, H. Yamada, T. Yajima, M. Harano, A. Takeuchi, K. Tatsugami, M. Hamaguchi, S. Naito, and Y. Yoshikai Donor CD4 T Cells Are Critical in Allogeneic Stem Cell Transplantation against Murine Solid Tumor Cancer Res., June 15, 2009; 69(12): 5151 - 5158. [Abstract] [Full Text] [PDF] A. Ghosh, W. Koestner, M. Hapke, V. Schlaphoff, F. Langer, R. Baumann, C. Koenecke, M. Cornberg, K. Welte, B. R. Blazar, et al. 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