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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2847-2857. Prepublished online as a Blood First Edition Paper on July 21, 2008; DOI 10.1182/blood-2008-01-132951. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-132951v1 112/7/2847    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 Hippen, K. L. Articles by Blazar, B. R. Search for Related Content PubMed PubMed Citation Articles by Hippen, K. L. Articles by Blazar, B. R. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells Keli L. Hippen1, Paul Harker-Murray1, Stephen B. Porter1, Sarah C. Merkel1, Aryel Londer1, Dawn K. Taylor1, Megan Bina1, Angela Panoskaltsis-Mortari1, Pablo Rubinstein2, Nico Van Rooijen3, Tatiana N. Golovina4, Megan M. Suhoski4, Jeffrey S. Miller5, John E. Wagner1, Carl H. June4, James L. Riley4, and Bruce R. Blazar1 1 University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone, Blood and Marrow Transplantation, Minneapolis; 2 National Cord Blood Program, The New York Blood Center, New York; 3 Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands; 4 Abramson Family Cancer Center Research Institute, University of Pennsylvania Cancer Center, Philadelphia; and 5 University of Minnesota Cancer Center and Department of Medicine, Division of Bone Marrow Transplantation, Minneapolis Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)–coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor β (TGF-β) secretion and the potency of Treg suppressor function. aAPCs modified to coexpress OX40L or 4-1BBL expanded UCB Tregs to a significantly greater extent than bead- or nonmodified aAPC cultures, reaching mean expansion levels exceeding 1250-fold. Despite the high expansion and in contrast to studies using other Treg sources, neither OX40 nor 4-1BB signaling of UCB Tregs reduced in vitro suppression. UCB Tregs expanded with 4-1BBL expressing aAPCs had decreased levels of proapoptotic bim. UCB Tregs expanded with nonmodified or modified aAPCs versus beads resulted in higher survival associated with increased Treg persistence in a xeno-geneic graft-versus-host disease lethality model. These data offer a novel approach for UCB Treg expansion using aAPCs, including those coexpressing OX40L or 4-1BBL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Zhao, Q. J. Wang, S. Yang, J. N. Kochenderfer, Z. Zheng, X. Zhong, M. Sadelain, Z. Eshhar, S. A. Rosenberg, and R. A. Morgan A Herceptin-Based Chimeric Antigen Receptor with Modified Signaling Domains Leads to Enhanced Survival of Transduced T Lymphocytes and Antitumor Activity J. Immunol., November 1, 2009; 183(9): 5563 - 5574. [Abstract] [Full Text] [PDF] L. C. Chen, J. C. Delgado, P. E. Jensen, and X. Chen Direct Expansion of Human Allospecific FoxP3+CD4+ Regulatory T Cells with Allogeneic B Cells for Therapeutic Application J. Immunol., September 15, 2009; 183(6): 4094 - 4102. [Abstract] [Full Text] [PDF]

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