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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1355-1361. Prepublished online as a Blood First Edition Paper on September 30, 2004; DOI 10.1182/blood-2004-08-3305. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3305v1 105/3/1355    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 Albert, M. H. Articles by Anasetti, C. Search for Related Content PubMed PubMed Citation Articles by Albert, M. H. Articles by Anasetti, C. Related Collections Immunobiology Transplantation Cell Cycle Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Prevention of lethal acute GVHD with an agonistic CD28 antibody and rapamycin Michael H. Albert, Xue-Zhong Yu, Paul J. Martin, and Claudio Anasetti From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine, University of Washington, Seattle. Successful hematopoietic cell transplantation (HCT) from an allogeneic donor ideally should produce tolerance to recipient alloantigens while preserving anti-infectious and antitumor immunity. Rapamycin together with costimulation blockade can induce tolerance in organ allograft models by inhibiting G1 S-phase progression and promoting T-cell apoptosis. In contrast to blocking costimulation through CD28, administration of agonistic CD28-specific antibody 37.51 partially prevents lethal graft-versus-host disease (GVHD) by selective depletion of alloreactive T cells in mice. We hypothesized that combining rapamycin with agonistic CD28 treatment would improve GVHD control by tolerizing a small subset of alloreactive T cells that might escape effects of the CD28-specific antibody. A short course of rapamycin plus agonistic CD28 treatment showed synergism at suboptimal doses, was highly effective in preventing lethal GVHD, and was superior to rapamycin plus CD28 blockade in a major histocompatibility complex class I– and II–mismatched HCT model. The combination treatment reduced the number of proliferating, alloreactive cells in the recipient, promoted donor B- and T-cell reconstitution, and reduced inflammatory cytokine levels. Administration of rapamycin plus agonistic CD28 antibodies offers a promising new therapeutic approach to facilitate tolerance after HCT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Mariotti, J. Foley, U. Jung, T. Borenstein, N. Kantardzic, S. Han, J. T. Hanson, E. Wong, N. Buxhoeveden, J. B. Trepel, et al. Ex Vivo Rapamycin Generates Apoptosis-Resistant Donor Th2 Cells That Persist In Vivo and Prevent Hemopoietic Stem Cell Graft Rejection J. Immunol., January 1, 2008; 180(1): 89 - 105. [Abstract] [Full Text] [PDF] R. Zeiser, D. B. Leveson-Gower, E. A. Zambricki, N. Kambham, A. Beilhack, J. Loh, J.-Z. Hou, and R. S. Negrin Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells Blood, January 1, 2008; 111(1): 453 - 462. [Abstract] [Full Text] [PDF] X.-Z. Yu, Y. Liang, R. I. Nurieva, F. Guo, C. Anasetti, and C. Dong Opposing Effects of ICOS on Graft-versus-Host Disease Mediated by CD4 and CD8 T Cells. J. Immunol., June 15, 2006; 176(12): 7394 - 7401. [Abstract] [Full Text] [PDF]

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