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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2215-2220. Prepublished online as a Blood First Edition Paper on May 31, 2005; DOI 10.1182/blood-2005-04-1391. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1391v1 106/6/2215    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 Westerhuis, G. Articles by Fibbe, W. E. Search for Related Content PubMed PubMed Citation Articles by Westerhuis, G. Articles by Fibbe, W. E. Related Collections Immunobiology Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Long-term mixed chimerism after immunologic conditioning and MHC-mismatched stem-cell transplantation is dependent on NK-cell tolerance Geert Westerhuis, Wendy G. E. Maas, Roel Willemze, René E. M. Toes, and Willem E. Fibbe From the Departments of Hematology and Rheumatology, Leiden University Medical Center, Leiden, The Netherlands T-cell tolerance is mandatory for major histocompatibility complex (MHC)-mismatched stem-cell transplantation without cytoreduction. Here, we used a cytotoxicity assay based on the infusion of differentially carboxyfluorescein succinimidyl ester (CFSE)-labeled syngeneic and donor splenocytes to determine the survival of donor cells in vivo. In vivo cytotoxicity data showed that treatment with anti-CD40 ligand monoclonal antibody in combination with a low dose of MHC-mismatched bone marrow cells was sufficient to induce T-cell tolerance. However, CFSE-labeled donor cells were still eliminated. A similar elimination pattern was observed in T-cell and natural killer T-cell (NKT-cell)-deficient mice, suggesting the involvement of natural killer (NK) cells. Indeed, in vivo NK-cell depletion resulted in a prolonged survival of CFSE-labeled donor cells, confirming the role of NK cells in this process. Transplantation of a megadose of MHC-mismatched bone marrow cells was required for a complete survival of CFSE-labeled donor cells. This NK-cell tolerance was donor specific and was associated with mixed chimerism. Additional NK-cell depletion significantly enhanced engraftment and allowed long-term chimerism after transplantation of a relatively low dose of donor bone marrow cells. These data demonstrate the importance of NK cells in the rejection of MHC-mismatched hematopoietic cells and may explain the high numbers of bone marrow cells required for transplantation over MHC barriers. (Blood. 2005;106:2215-2220) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Chimera: from bane to blessing Dan L. Longo Blood 2005 106: 1890-1891. [Full Text] [PDF] This article has been cited by other articles: D. M. Miller, T. B. Thornley, T. Pearson, A. J. Kruger, M. Yamazaki, L. D. Shultz, R. M. Welsh, M. A. Brehm, A. A. Rossini, and D. L. Greiner TLR Agonists Prevent the Establishment of Allogeneic Hematopoietic Chimerism in Mice Treated with Costimulation Blockade J. Immunol., May 1, 2009; 182(9): 5547 - 5559. [Abstract] [Full Text] [PDF] E. T. Durkin, K. A. Jones, D. Rajesh, and A. F. Shaaban Early chimerism threshold predicts sustained engraftment and NK-cell tolerance in prenatal allogeneic chimeras Blood, December 15, 2008; 112(13): 5245 - 5253. [Abstract] [Full Text] [PDF] R. A. Cahill, D. Wenkert, S. A. Perlman, A. Steele, S. P. Coburn, W. H. McAlister, S. Mumm, and M. P. Whyte Infantile Hypophosphatasia: Transplantation Therapy Trial Using Bone Fragments and Cultured Osteoblasts J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2923 - 2930. [Abstract] [Full Text] [PDF] R. Flierman, G. Westerhuis, M. Hameetman, L. M. van Duivenvoorde, T. van Hall, J. M. van Laar, W. E. Fibbe, and R. E. M. Toes Targeting host B-cell immune responses by persistent donor NK-cell alloreactivity following nonmyeloablative allogeneic stem cell transplantation Blood, June 15, 2007; 109(12): 5524 - 5525. [Full Text] [PDF] A. J. Nauta, G. Westerhuis, A. B. Kruisselbrink, E. G. A. Lurvink, R. Willemze, and W. E. Fibbe Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting Blood, September 15, 2006; 108(6): 2114 - 2120. [Abstract] [Full Text] [PDF]

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