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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1703-1711. Prepublished online as a Blood First Edition Paper on November 15, 2005; DOI 10.1182/blood-2005-08-3445. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3445v1 107/4/1703    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 Waldman, E. Articles by van den Brink, M. R. M. Search for Related Content PubMed PubMed Citation Articles by Waldman, E. Articles by van den Brink, M. R. M. Related Collections Transplantation Cell Adhesion and Motility Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Absence of 7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine Elisha Waldman, Sydney X. Lu, Vanessa M. Hubbard, Adam A. Kochman, Jeffrey M. Eng, Theis H. Terwey, Stephanie J. Muriglan, Theo D. Kim, Glenn Heller, George F. Murphy, Chen Liu, Onder Alpdogan, and Marcel R. M. van den Brink From the Departments of Medicine and Immunology, Pediatrics, and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; the Department of Pathology, Brigham and Women's Hospital, Boston, MA; and the Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL. The 47 integrin plays a central role in the homing of T cells to the gut. We hypothesized that absence of the 7 subunit would result in a reduction of intestinal graft-versus-host disease (GVHD) and an improvement in overall GVHD morbidity and mortality in recipients of hematopoietic stem cell transplantation (HSCT). Analysis of alloreactive 7-/- T cells showed intact activation, proliferation, cytokine production, and cytotoxicity. However, recipients of 7-/- donor T cells in murine HSCT models experienced less GVHD morbidity and mortality than recipients of wild-type (WT) T cells, associated with a decrease in donor T-cell infiltration of the liver and intestine and with an overall significant decrease in hepatic and intestinal GVHD. In graft-versus-tumor (GVT) experiments, we demonstrated intact or even enhanced GVT activity of 7-/- donor T cells. In conclusion, 7-/- donor T cells caused less GVHD morbidity and mortality than WT donor T cells because of selectively decreased T-cell infiltration of the liver and intestines. Our data suggest that strategies to target the 7 integrin have the clinical potential to alleviate or prevent GVHD while sparing or potentiating GVT activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. K. Jasperson, C. Bucher, A. Panoskaltsis-Mortari, P. A. Taylor, A. L. Mellor, D. H. Munn, and B. R. Blazar Indoleamine 2,3-dioxygenase is a critical regulator of acute graft-versus-host disease lethality Blood, March 15, 2008; 111(6): 3257 - 3265. [Abstract] [Full Text] [PDF] T. D. Kim, T. H. Terwey, J. L. Zakrzewski, D. Suh, A. A. Kochman, M. E. Chen, C. G. King, C. Borsotti, J. Grubin, O. M. Smith, et al. Organ-derived dendritic cells have differential effects on alloreactive T cells Blood, March 1, 2008; 111(5): 2929 - 2940. [Abstract] [Full Text] [PDF] M. Marski, A. L. Ye, and C. Abraham CD18 Is Required for Intestinal T Cell Responses at Multiple Immune Checkpoints J. Immunol., February 15, 2007; 178(4): 2104 - 2112. [Abstract] [Full Text] [PDF] C. Zhang, J. Lou, N. Li, I. Todorov, C.-L. Lin, Y.-A. Cao, C. H. Contag, F. Kandeel, S. Forman, and D. Zeng Donor CD8+ T Cells Mediate Graft-versus-Leukemia Activity without Clinical Signs of Graft-versus-Host Disease in Recipients Conditioned with Anti-CD3 Monoclonal Antibody J. Immunol., January 15, 2007; 178(2): 838 - 850. [Abstract] [Full Text] [PDF]

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