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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1828-1836. Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-08-3213. This Article Full Text (PDF) All Versions of this Article: 2004-08-3213v1 105/4/1828    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 Hanash, A. M Articles by Levy, R. B Search for Related Content PubMed PubMed Citation Articles by Hanash, A. M Articles by Levy, R. B Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 19, 2004 Accepted October 8, 2004 Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC mismatched hematopoietic cell transplantation Alan M Hanash and Robert B Levy* Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL, USA * Corresponding author; email: rlevy{at}med.miami.edu. Allogeneic bone marrow transplantation (BMT) is a potentially curative treatment for both inherited and acquired diseases of the hematopoietic compartment; however, its wider use is limited by the frequent and severe outcome of graft vs. host disease (GVHD). Unfortunately, efforts to reduce GVHD by removing donor T-cells have resulted in poor engraftment and elevated disease recurrence. Alternative cell populations capable of supporting allogeneic hematopoietic stem/progenitor cell engraftment without inducing GVHD could increase numbers of potential recipients while broadening the pool of acceptable donors. Although unfractionated CD4+ T cells have not been shown to be an efficient facilitating population, CD4+CD25+ regulatory (T-reg) cells were examined for their capacity to support allogeneic hematopoietic engraftment. In a murine fully MHC-mismatched BMT model, co-transplantation of donor B6 T-regs into sublethally conditioned BALB/c recipients supported significantly greater lineage committed and multi-potential donor progenitors in recipient spleens one week post-transplant and significantly increased long-term multi-lineage donor chimerism. Donor engraftment occurred without GVHD-related weight loss or lethality and was associated with tolerance to donor and host antigens by in vitro and in vivo analyses. Donor CD4+CD25+ T cells may therefore represent a potential alternative to unfractionated T cells for promotion of allogeneic engraftment in clinical hematopoietic cell. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: CD4+CD25+ T cells, transplant engraftment, and allospecific tolerance Giovanna Lombardi Blood 2005 105: 1375-1376. [Full Text] [PDF] This article has been cited by other articles: B. Blanco, J. A. Perez-Simon, L. I. Sanchez-Abarca, T. Caballero-Velazquez, S. Gutierrez-Cossio, P. Hernandez-Campo, M. Diez-Campelo, C. Herrero-Sanchez, C. Rodriguez-Serrano, C. Santamaria, et al. Treatment with bortezomib of human CD4+ T cells preserves natural regulatory T cells and allows the emergence of a distinct suppressor T-cell population Haematologica, July 1, 2009; 94(7): 975 - 983. [Abstract] [Full Text] [PDF] O. Bohana-Kashtan, S. Morisot, R. Hildreth, C. Brayton, H. I. Levitsky, and C. I. Civin Selective Reduction of Graft-versus-Host Disease-Mediating Human T Cells by Ex Vivo Treatment with Soluble Fas Ligand J. Immunol., July 1, 2009; 183(1): 696 - 705. [Abstract] [Full Text] [PDF] A. L. Bayer, M. Jones, J. Chirinos, L. de Armas, T. H. Schreiber, T. R. Malek, and R. B. Levy Host CD4+CD25+ T cells can expand and comprise a major component of the Treg compartment after experimental HCT Blood, January 15, 2009; 113(3): 733 - 743. [Abstract] [Full Text] [PDF] J. Mariotti, J. Foley, K. Ryan, N. Buxhoeveden, V. Kapoor, S. Amarnath, and D. H. Fowler Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway Blood, December 1, 2008; 112(12): 4765 - 4775. [Abstract] [Full Text] [PDF] P. Verginis, K. A. McLaughlin, K. W. Wucherpfennig, H. von Boehmer, and I. Apostolou Induction of antigen-specific regulatory T cells in wild-type mice: Visualization and targets of suppression PNAS, March 4, 2008; 105(9): 3479 - 3484. [Abstract] [Full Text] [PDF] M. C. Ruzek, J. S. Waire, D. Hopkins, G. LaCorcia, J. Sullivan, B. L. Roberts, S. M. Richards, S. R. Nahill, J. M. Williams, A. Scaria, et al. Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo Blood, February 1, 2008; 111(3): 1726 - 1734. [Abstract] [Full Text] [PDF] J.-G. Chai, D. Coe, D. Chen, E. Simpson, J. Dyson, and D. Scott In Vitro Expansion Improves In Vivo Regulation by CD4+CD25+ Regulatory T Cells J. Immunol., January 15, 2008; 180(2): 858 - 869. [Abstract] [Full Text] [PDF] 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] K. N. Taylor, V. R. Shinde-Patil, E. Cohick, and Y. L. Colson Induction of FoxP3+CD4+25+ Regulatory T Cells Following Hemopoietic Stem Cell Transplantation: Role of Bone Marrow-Derived Facilitating Cells J. Immunol., August 15, 2007; 179(4): 2153 - 2162. [Abstract] [Full Text] [PDF] L. Weng, J. Dyson, and F. Dazzi Low-intensity transplant regimens facilitate recruitment of donor-specific regulatory T cells that promote hematopoietic engraftment PNAS, May 15, 2007; 104(20): 8415 - 8420. [Abstract] [Full Text] [PDF] C. Pabst, H. Schirutschke, G. Ehninger, M. Bornhauser, and U. Platzbecker The Graft Content of Donor T Cells Expressing {gamma}{delta}TCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors Clin. Cancer Res., May 15, 2007; 13(10): 2916 - 2922. [Abstract] [Full Text] [PDF] P. Hoffmann, R. Eder, T. J. Boeld, K. Doser, B. Piseshka, R. Andreesen, and M. Edinger Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion Blood, December 15, 2006; 108(13): 4260 - 4267. [Abstract] [Full Text] [PDF] D. Adeegbe, A. L. Bayer, R. B. Levy, and T. R. Malek Cutting Edge: Allogeneic CD4+CD25+Foxp3+ T Regulatory Cells Suppress Autoimmunity while Establishing Transplantation Tolerance. J. Immunol., June 15, 2006; 176(12): 7149 - 7153. [Abstract] [Full Text] [PDF] I. Barao, A. M. Hanash, W. Hallett, L. A. Welniak, K. Sun, D. Redelman, B. R. Blazar, R. B. Levy, and W. J. Murphy Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells PNAS, April 4, 2006; 103(14): 5460 - 5465. [Abstract] [Full Text] [PDF] K. Rieger, C. Loddenkemper, J. Maul, T. Fietz, D. Wolff, H. Terpe, B. Steiner, E. Berg, S. Miehlke, M. Bornhauser, et al. Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD Blood, February 15, 2006; 107(4): 1717 - 1723. [Abstract] [Full Text] [PDF] C. A. Wysocki, Q. Jiang, A. Panoskaltsis-Mortari, P. A. Taylor, K. P. McKinnon, L. Su, B. R. Blazar, and J. S. Serody Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease Blood, November 1, 2005; 106(9): 3300 - 3307. [Abstract] [Full Text] [PDF] B. R Blazar and W. J Murphy Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD) Phil Trans R Soc B, September 29, 2005; 360(1461): 1747 - 1767. [Abstract] [Full Text] [PDF]

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