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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1671-1678. Prepublished online as a Blood First Edition Paper on May 27, 2004; DOI 10.1182/blood-2004-03-1115. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1115v1 104/6/1671    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 Chen, J. Articles by Young, N. S. Search for Related Content PubMed PubMed Citation Articles by Chen, J. Articles by Young, N. S. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Bystander destruction of hematopoietic progenitor and stem cells in a mouse model of infusion-induced bone marrow failure Jichun Chen, Karen Lipovsky, Felicia M. Ellison, Rodrigo T. Calado, and Neal S. Young From the Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Infusion of parental lymph node (LN) cells into sublethally irradiated hybrid F1 recipients created a murine model for bone marrow (BM) failure. Affected animals developed fatal pancytopenia within 2 to 3 weeks, accompanied by BM oligoclonal T-cell infiltration and severe marrow hypoplasia indicated by approximately 10-fold declines in total BM cellularity, 15-fold declines in BM Lin-Sca1+c-Kit+ cells, 100-fold declines in spleen colony-forming units, and 100-fold declines in hematopoietic progenitor and stem cells as estimated by irradiation protection in vivo. LN cells of both H2b/b and H2d/d haplotypes were effectors. Serum interferon- (IFN-) concentration increased 2- to 3-fold. Marrow cells were severely apoptotic, with high proportions of Fas+ and annexin V+ cells. Cotransplantation of 5 x 105 BM cells from clinically affected donors and 106 BM cells from H2 identical healthy mice could not rescue lethally irradiated recipients. Recipients had significantly lower cellularity in peripheral blood and BM, and cell mixtures failed to produce a stromal feeder layer to support marrow cell growth in vitro. Pathogenic T cells from donors after BM failure appeared capable of destroying hematopoietic progenitor, stem, and stromal cells from fully compatible healthy donors as "innocent bystanders." This effect can be partially abrogated by anti-IFN- antibody. (Blood. 2004;104:1671-1678) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. J. Stotler, B. Eghtesad, E. Hsi, and B. Silver Rapid resolution of GVHD after orthotopic liver transplantation in a patient treated with alefacept Blood, May 21, 2009; 113(21): 5365 - 5366. [Full Text] [PDF] S. O. Omokaro, M. J. Desierto, M. A. Eckhaus, F. M. Ellison, J. Chen, and N. S. Young Lymphocytes with Aberrant Expression of Fas or Fas Ligand Attenuate Immune Bone Marrow Failure in a Mouse Model J. Immunol., March 15, 2009; 182(6): 3414 - 3422. [Abstract] [Full Text] [PDF] J.-S. Delisle, L. Gaboury, M.-P. Belanger, E. Tasse, H. Yagita, and C. Perreault Graft-versus-host disease causes failure of donor hematopoiesis and lymphopoiesis in interferon-{gamma} receptor-deficient hosts Blood, September 1, 2008; 112(5): 2111 - 2119. [Abstract] [Full Text] [PDF] B. Verbinnen, A. D. Billiau, J. Vermeiren, G. Galicia, D. M. A. Bullens, L. Boon, P. Cadot, G. Hens, C. Dewolf-Peeters, S. W. Van Gool, et al. Contribution of Regulatory T Cells and Effector T Cell Deletion in Tolerance Induction by Costimulation Blockadel J. Immunol., July 15, 2008; 181(2): 1034 - 1042. [Abstract] [Full Text] [PDF] J. Chen, F. M. Ellison, M. A. Eckhaus, A. L. Smith, K. Keyvanfar, R. T. Calado, and N. S. Young Minor Antigen H60-Mediated Aplastic Anemia Is Ameliorated by Immunosuppression and the Infusion of Regulatory T Cells J. Immunol., April 1, 2007; 178(7): 4159 - 4168. [Abstract] [Full Text] [PDF] N. S. Young, R. T. Calado, and P. Scheinberg Current concepts in the pathophysiology and treatment of aplastic anemia Blood, October 15, 2006; 108(8): 2509 - 2519. [Abstract] [Full Text] [PDF] N. S. Young Pathophysiologic Mechanisms in Acquired Aplastic Anemia Hematology, January 1, 2006; 2006(1): 72 - 77. [Abstract] [Full Text] [PDF] J. Chen and N. S. Young A Murine Model of Bone Marrow Failure Mediated by Disparity in Minor Histocompatibility Antigens. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 132 - 132. [Abstract] M. P. Westerman, A. Pizzey, J. Hirshman, M. Cerino, A. Eze, A. Lawrie, G. Purdie, I. Mackie, and J. Porter Hydroxyurea Treated Sickle Disorders Demonstrate Decreased Plasma Hb, Red Cell Vesicles and Thrombolysis. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 2322 - 2322. [Abstract] A. M. Risitano New Challenges to Developing Animal Models for Human Immune-Mediated Marrow Failure Clin. Med. Res., May 1, 2005; 3(2): 63 - 64. [Full Text] [PDF] J. 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