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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4755-4764. Prepublished online as a Blood First Edition Paper on September 24, 2008; DOI 10.1182/blood-2008-02-142737. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-142737v1 112/12/4755    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 Citing Articles via Google Scholar Google Scholar Articles by Alpdogan, S. O. Articles by van den Brink, M. R. M. Search for Related Content PubMed PubMed Citation Articles by Alpdogan, S. O. Articles by van den Brink, M. R. M. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Rapidly proliferating CD44hi peripheral T cells undergo apoptosis and delay posttransplantation T-cell reconstitution after allogeneic bone marrow transplantation S. Önder Alpdogan1,2, Sydney X. Lu1,*, Neel Patel1,*, Suzanne McGoldrick1, David Suh1, Tulin Budak-Alpdogan3, Odette M. Smith1, Jeremy Grubin1, Christopher King1, Gabrielle L. Goldberg1, Vanessa M. Hubbard1,4, Adam A. Kochman1, and Marcel R. M. van den Brink1 1 Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY; 2 Department of Medicine, Yale University School of Medicine, New Haven, CT; 3 Department of Medicine, Cancer Institute of New Jersey, New Brunswick; and 4 Department of Pathology, Albert Einstein College of Medicine, Bronx, NY Delayed T-cell recovery is an important complication of allogeneic bone marrow transplantation (BMT). We demonstrate in murine models that donor BM-derived T cells display increased apoptosis in recipients of allogeneic BMT with or without GVHD. Although this apoptosis was associated with a loss of Bcl-2 and Bcl-XL expression, allogeneic recipients of donor BM deficient in Fas-, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)- or Bax-, or BM-overexpressing Bcl-2 or Akt showed no decrease in apoptosis of peripheral donor-derived T cells. CD44 expression was associated with an increased percentage of BM-derived apoptotic CD4+ and CD8+ T cells. Transplantation of RAG-2-eGFP–transgenic BM revealed that proliferating eGFPloCD44hi donor BM-derived mature T cells were more likely to undergo to apoptosis than nondivided eGFPhiCD44lo recent thymic emigrants in the periphery. Finally, experiments using carboxyfluorescein succinimidyl ester–labeled T cells adoptively transferred into irradiated syngeneic hosts revealed that rapid spontaneous proliferation (as opposed to slow homeostatic proliferation) and acquisition of a CD44hi phenotype was associated with increased apoptosis in T cells. We conclude that apoptosis of newly generated donor-derived peripheral T cells after an allogeneic BMT contributes to delayed T-cell reconstitution and is associated with CD44 expression and rapid spontaneous proliferation by donor BM-derived T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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