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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5734-5744. Prepublished online as a Blood First Edition Paper on March 11, 2008; DOI 10.1182/blood-2008-01-136531. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-136531v1 111/12/5734    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kelly, R. M Articles by Blazar, B. R Search for Related Content PubMed PubMed Citation Articles by Kelly, R. M Articles by Blazar, B. R Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 29, 2008 Accepted March 8, 2008 Keratinocyte growth factor and androgen blockade work in concert to protect against conditioning regimen-induced thymic epithelial damage and enhance T-cell reconstitution following murine bone marrow transplantation Ryan M Kelly, Steven L Highfill, Angela Panoskaltsis-Mortari, Patricia A Taylor, Richard L Boyd, Georg A Hollander, and Bruce R Blazar* Division of Hematology, Oncology and Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, United States Walter and Eliza Hall Institute, Victoria, Australia Department of Clinical-Biological Sciences, Laboratory of Pediatric Immunology, University of Basel, Basel University Children's Hospital (UKBB), Basel, Switzerland * Corresponding author; email: blaza001{at}umn.edu. Myeloablative conditioning results in thymic epithelial cell (TEC) injury, slow T-cell reconstitution, and a high risk of opportunistic infections. Keratinocyte growth factor (KGF) stimulates TEC proliferation and, when given pre-conditioning, reduces TEC injury. Thymocytes and TEC express androgen receptors and exposure to androgen inhibits thymopoiesis. In this study, we have investigated whether TEC stimulation via pre-conditioning treatment with KGF and leuprolide acetate (LupronTM), two clinically approved agents, given only prior to conditioning would circumvent the profound TEC and associated T-cell deficiency seen in allogeneic bone marrow transplant (BMT) recipients. Only combined treatment with KGF plus Lupron normalized TEC subset numbers and thymic architecture. Thymopoiesis and thymic output were supranormal, leading to the accelerated peripheral reconstitution of naive CD4 and CD8 T-cells with a broad V repertoire and decreased homeostatic T-cell proliferation. Combined therapy facilitated T:B cooperativity and enabled a B-cell humoral response to a CD4 T-cell dependent neoantigen challenge early post-BMT. In vivo antigen-specific CD8 T-cell responses and clearance of a live pathogen was superior with combined versus individual agent therapy. Thus, KGF combined with androgen blockade represent a novel approach to restore thymic function and facilitates the rapid recovery of peripheral T-cell function following allogeneic BMT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: High-TECh thymus Eugene Kwon Blood 2008 111: 5421-5422. [Full Text] [PDF] This article has been cited by other articles: G. L. Goldberg, C. G. King, R. A. Nejat, D. Y. Suh, O. M. Smith, J. C. Bretz, R. M. Samstein, J. A. Dudakov, A. P. Chidgey, S. Chen-Kiang, et al. Luteinizing Hormone-Releasing Hormone Enhances T Cell Recovery following Allogeneic Bone Marrow Transplantation J. Immunol., May 1, 2009; 182(9): 5846 - 5854. [Abstract] [Full Text] [PDF]

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