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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3884-3892. Prepublished online as a Blood First Edition Paper on January 25, 2008; DOI 10.1182/blood-2007-11-125294. This Article Full Text (PDF) All Versions of this Article: blood-2007-11-125294v1 111/7/3884    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 Matte-Martone, C. Articles by Shlomchik, W. D. Search for Related Content PubMed PubMed Citation Articles by Matte-Martone, C. Articles by Shlomchik, W. D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 28, 2007 Accepted January 13, 2008 CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL Catherine Matte-Martone, Jinli Liu, Dhanpat Jain, Jennifer McNiff, and Warren D. Shlomchik* Section of Medical Oncology, Cancer Center, Yale University School of Medicine, New Haven, CT, United States Department of Pathology, Hartford Hospital, Hartford, CT, United States Department of Pathology, Yale University School of Medicine, New Haven, CT, United States Department of Dermatology, Yale University School of Medicine, New Haven, CT, United States Department of Immunobiology, Yale University School of Medicine, New Haven, CT, United States * Corresponding author; email: warren.shlomchik{at}yale.edu. Whether T cell antigen receptors (TCR) on donor T cells require direct interactions with major histocompatibility complex class I or class II (MHCI/II) molecules on target cells to mediate GVHD and GVL is a fundamental question in allogeneic stem cell transplantation (alloSCT). In MHC-mismatched mouse models, these contacts were not required for GVHD. However, this conclusion may not apply to MHC-matched, multiple minor histocompatibility antigen-mismatched alloSCT, the most common type performed clinically. To address this we used wild type (wt)MHCI-/- or wtMHCII-/- bone marrow chimeras as recipients in GVHD experiments. For GVL experiments we used MHCI-/- or MHCII-/- chronic phase CML cells created by expressing the bcr-abl cDNA in bone marrow from MHCI-/- or MHCII-/- mice. TCR:MHCI contact was obligatory for both CD8-mediated GVHD and GVL. In contrast, CD4 cells induced GVHD in wtMHCII-/- chimeras whereas MHCII-/- mCP-CML was GVL-resistant. Donor CD4 cells infiltrated affected skin and bowel in wtMHCII-/- recipients indicating that they mediated GVHD by acting locally. Thus CD4 cells employ distinct effector mechanisms in GVHD and GVL: direct cytolytic action is required for GVL but not for GVHD. If these noncytolytic pathways can be inhibited, then GVHD might be ameliorated while preserving GVL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Sun, M. Li, T. J. Sayers, L. A. Welniak, and W. J. Murphy Differential effects of donor T-cell cytokines on outcome with continuous bortezomib administration after allogeneic bone marrow transplantation Blood, August 15, 2008; 112(4): 1522 - 1529. [Abstract] [Full Text] [PDF]

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