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Blood, 15 January 2008, Vol. 111, No. 2, pp. 954-962. Prepublished online as a Blood First Edition Paper on October 10, 2007; DOI 10.1182/blood-2007-05-089573. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-089573v1 111/2/954    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 CrossRef Google Scholar Articles by Liang, Y. Articles by Yu, X.-Z. PubMed PubMed Citation Articles by Liang, Y. Articles by Yu, X.-Z. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects Yaming Liang1, Chen Liu2, Julie Y. Djeu1,3, Bin Zhong1, Thorsten Peters4, Karin Scharffetter-Kochanek4, Claudio Anasetti1,3, and Xue-Zhong Yu1,3 1 H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; 2 Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville; 3 Department of Interdisciplinary Oncology, University of South Florida, Tampa; and 4 Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg, Germany Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation. Migration of donor-derived T cells into GVHD target organs plays an essential role in the development of GVHD. β2 integrins are critically important for leukocyte extravasation through vascular endothelia and for T-cell activation. We asked whether CD18-deficient T cells would induce less GVHD while sparing the graft-versus-leukemia (GVL) effect. In murine allogeneic bone marrow transplantation models, we found that recipients of CD18–/– donor T cells had significantly less GVHD morbidity and mortality compared with recipients of wild-type (WT) donor T cells. Analysis of alloreactivity showed that CD18–/– and WT T cells had comparable activation, expansion, and cytokine production in vivo. Reduced GVHD was associated with a significant decrease in donor T-cell infiltration of recipient intestine and with an overall decrease in pathologic scores in intestine and liver. Finally, we found that the in vivo GVL effect of CD18–/– donor T cells was largely preserved, because mortality of the recipients who received transplants of CD18–/– T cells plus tumor cells was greatly delayed or prevented. Our data suggest that strategies to target β2 integrin have clinical potential to alleviate or prevent GVHD while sparing GVL activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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