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Blood, 1 August 2004, Vol. 104, No. 3, pp. 873-880. Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2003-11-3910. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3910v1 104/3/873    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 Huang, Y. Articles by Ildstad, S. T. Search for Related Content PubMed PubMed Citation Articles by Huang, Y. Articles by Ildstad, S. T. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment Yiming Huang, Francine Rezzoug, Paula M. Chilton, H. Leighton Grimes, Daniel E. Cramer, and Suzanne T. Ildstad From the Institute for Cellular Therapeutics and the Department of Surgery, University of Louisville, Louisville, KY. The events that regulate engraftment and long-term repopulating ability of hematopoietic stem cells (HSCs) after transplantation are not well defined. We report for the first time that major histocompatibility complex (MHC) class I K plays a critical role in HSC engraftment via interaction with recipient natural killer (NK) cells. Durable engraftment of purified HSCs requires MHC class I K matching between HSC donor and recipient. In the absence of MHC class I K matching, HSCs exhibit impaired long-term engraftment (P = .01). Dependence on MHC class I K matching is eliminated in B6 beige mice that lack NK cell function, as well as in wild-type mice depleted of NK cells, implicating a possible regulatory role of NK cells for HSC engraftment. The coadministration of CD8+/T-cell receptor–negative (TCR-) graft facilitating cells (FCs) matched at MHC class I K to the HSC donor overcomes the requirement for MHC class I K matching between HSCs and recipient. These data demonstrate that FCs inhibit NK cell effects on the HSCs. Notably, FCs do not suppress the cytotoxic activity of activated NK cells. Enhanced green fluorescent protein–positive (EGFP+) FCs persist for one month following allogeneic transplantation, making cold target inhibition an unlikely mechanism. Therefore, MHC class I may play a critical role in the initiating events that dictate HSC engraftment and/or NK-mediated rejection following allogeneic transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Hayakawa, M. M. Hsieh, N. Uchida, O. Phang, and J. F. Tisdale Busulfan Produces Efficient Human Cell Engraftment in NOD/LtSz-Scid IL2R{gamma}Null Mice Stem Cells, January 1, 2009; 27(1): 175 - 182. [Abstract] [Full Text] [PDF] F. Rezzoug, Y. Huang, M. K. Tanner, M. Wysoczynski, C. L. Schanie, P. M. Chilton, M. Z. Ratajczak, I. J. Fugier-Vivier, and S. T. Ildstad TNF-{alpha} Is Critical to Facilitate Hemopoietic Stem Cell Engraftment and Function J. Immunol., January 1, 2008; 180(1): 49 - 57. [Abstract] [Full Text] [PDF] H. Xu, P. M. Chilton, M. K. Tanner, Y. Huang, C. L. Schanie, M. Dy-Liacco, J. Yan, and S. T. Ildstad Humoral immunity is the dominant barrier for allogeneic bone marrow engraftment in sensitized recipients Blood, November 15, 2006; 108(10): 3611 - 3619. [Abstract] [Full Text] [PDF] Y. Huang, M. Kucia, F. Rezzoug, J. Ratajczak, M. K. Tanner, M. Z. Ratajczak, C. L. Schanie, H. Xu, I. Fugier-Vivier, and S. T. Ildstad Flt3-Ligand-Mobilized Peripheral Blood, but Not Flt3-Ligand-Expanded Bone Marrow, Facilitating Cells Promote Establishment of Chimerism and Tolerance Stem Cells, April 1, 2006; 24(4): 936 - 948. [Abstract] [Full Text] [PDF] Y. Huang, F. Rezzoug, H. Xu, P. M. Chilton, C. L. Schanie, I. Fugier-Vivier, and S. T. Ildstad NK Cells Play a Critical Role in the Regulation of Class I-Deficient Hemopoietic Stem Cell Engraftment: Evidence for NK Tolerance Correlates with Receptor Editing J. Immunol., September 15, 2005; 175(6): 3753 - 3761. [Abstract] [Full Text] [PDF] P. M. Chilton, F. Rezzoug, M. Z. Ratajczak, I. Fugier-Vivier, J. Ratajczak, M. Kucia, Y. Huang, M. K. Tanner, and S. T. Ildstad Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients Blood, March 1, 2005; 105(5): 2189 - 2197. [Abstract] [Full Text] [PDF] I. J. Fugier-Vivier, F. Rezzoug, Y. Huang, A. J. Graul-Layman, C. L. Schanie, H. Xu, P. M. Chilton, and S. T. Ildstad Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment J. Exp. Med., February 7, 2005; 201(3): 373 - 383. [Abstract] [Full Text] [PDF]

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