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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5242-5251. Prepublished online as a Blood First Edition Paper on February 19, 2008; DOI 10.1182/blood-2007-09-107953. This Article Full Text (PDF) All Versions of this Article: blood-2007-09-107953v1 111/10/5242    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Anderson, B. E. Articles by Shlomchik, M. J. Search for Related Content PubMed PubMed Citation Articles by Anderson, B. E. Articles by Shlomchik, M. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 5, 2007 Accepted February 16, 2008 Effects of donor T cell trafficking and priming site on GVHD induction by naive and memory phenotype CD4 T cells Britt E. Anderson, Patricia A. Taylor, Jennifer M. McNiff, Dhanpat Jain, Anthony J. Demetris, Angela Panoskaltsis-Mortari, Ann Ager, Bruce R. Blazar, Warren D. Shlomchik, and Mark J. Shlomchik* Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, United States Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN, United States Department of Pathology and Dermatology, Yale University School of Medicine, New Haven, CT, United States Department of Pathology, Yale University School of Medicine, New Haven, CT, United States Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, United Kingdom Section of Medical Oncology and Department of Immunobiology, Yale University School of Medicine, New Haven, CT, United States Department of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT, United States * Corresponding author; email: mark.shlomchik{at}yale.edu. Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Effector memory T cells (TEM) do not cause GVHD but engraft and mount immune responses, including graft-vs.-tumor effects. One potential explanation for the inability of TEM to cause GVHD is that TEM lack CD62L and CCR7, which are instrumental in directing naive T cells (TN) to lymph nodes (LN) and Peyers patches (PP), putative sites of GVHD initiation. Thus TEM should be relatively excluded from LN and PP, possibly explaining their inability to cause GVHD. We tested this hypothesis using T cells deficient in CD62L or CCR7, transplant recipients lacking PNAd ligands for CD62L, and recipients without LN, PP or LN, PP and spleen. Surprisingly, CD62L and CCR7 were not required for TN-mediated GVHD. Moreover, in multiple strain pairings GVHD developed in recipients that lacked LN and PP. Mild GVHD could even be induced in mice lacking all major secondary lymphoid tissues (SLT). Conversely, enforced constitutive expression of CD62L on TEM did not endow them with the ability to cause GVHD. Taken together, these data argue against the hypothesis that TEM fail to induce GVHD because of inefficient trafficking to LN and PP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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