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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3983-3991. Prepublished online as a Blood First Edition Paper on January 24, 2006; DOI 10.1182/blood-2005-10-4201. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-4201v1 107/10/3983    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 Solomou, E. E. Articles by Young, N. S. Search for Related Content PubMed PubMed Citation Articles by Solomou, E. E. Articles by Young, N. S. Related Collections Hematopoiesis and Stem Cells Immunobiology Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY T-bet, a Th1 transcription factor, is up-regulated in T cells from patients with aplastic anemia Elena E. Solomou, Keyvan Keyvanfar, and Neal S. Young From the Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD. In aplastic anemia, immune destruction of hematopoietic cells results in bone marrow failure. Type 1 cytokines, especially IFN-, have been implicated in the pathophysiology of T-cell–mediated, Fas-mediated stem cell apoptosis of hematopoietic cells. Here, we show that the transcription factor T-bet (T-box expressed in T cells) is increased in T cells from patients with aplastic anemia. Patients' T-bet bound directly to the proximal site of the IFN- promoter without any prior stimulation, in contrast to healthy controls. Increased levels of Itk kinase participated in T-bet up-regulation and active transcription of the IFN- gene observed in these patients. Blocking PKC-, a kinase that lies downstream of Itk kinase, decreased T-bet protein and IFN- intracellular levels. These data suggest that the increased IFN- levels observed in aplastic anemia patients are the result of active transcription of the IFN- gene by T-bet. Blocking the transcription of the IFN- gene with kinase inhibitors might lead to the development of novel therapeutic agents for patients with aplastic anemia and other autoimmune diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Takamatsu, J. L. Espinoza, X. Lu, Z. Qi, K. Okawa, and S. Nakao Anti-Moesin Antibodies in the Serum of Patients with Aplastic Anemia Stimulate Peripheral Blood Mononuclear Cells to Secrete TNF-{alpha} and IFN-{gamma} J. Immunol., January 1, 2009; 182(1): 703 - 710. [Abstract] [Full Text] [PDF] Y. Tang, J. Chen, and N. Young Critical Role of the Th1 Transcription Factor T-Bet in An Animal Model of Immune-Mediated Bone Marrow Failure Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 1037 - 1037. [Abstract] X. Feng, S. Kajigaya, E. E. Solomou, K. Keyvanfar, X. Xu, N. Raghavachari, P. J. Munson, T. M. Herndon, J. Chen, and N. S. Young Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro Blood, April 1, 2008; 111(7): 3675 - 3683. [Abstract] [Full Text] [PDF] E. E. Solomou, K. Rezvani, S. Mielke, D. Malide, K. Keyvanfar, V. Visconte, S. Kajigaya, A. J. Barrett, and N. S. Young Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia Blood, September 1, 2007; 110(5): 1603 - 1606. [Abstract] [Full Text] [PDF] E. E. Solomou, F. Gibellini, B. Stewart, D. Malide, M. Berg, V. Visconte, S. Green, R. Childs, S. J. Chanock, and N. S. Young Perforin gene mutations in patients with acquired aplastic anemia Blood, June 15, 2007; 109(12): 5234 - 5237. [Abstract] [Full Text] [PDF] E. M. Sloand, L. Pfannes, G. Chen, S. Shah, E. E. Solomou, J. Barrett, and N. S. Young CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins Blood, March 15, 2007; 109(6): 2399 - 2405. [Abstract] [Full Text] [PDF] A. Bacigalupo Aplastic Anemia: Pathogenesis and Treatment Hematology, January 1, 2007; 2007(1): 23 - 28. [Abstract] [Full Text] [PDF] E. E. Solomou, V. Visconte, F. Gibellini, and N. S. Young SAP (SH2D1A), the Immunomodulator Deficient in X-Linked Lymphoproliferative Syndrome (XLP), Is Profoundly Decreased in Aplastic Anemia: An Immunologic Link between Constitutional and Acquired Bone Marrow Failure. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 1141 - 1141. [Abstract] [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] E. M. Sloand, A. S. M. Yong, S. Ramkissoon, E. Solomou, T. C. Bruno, S. Kim, M. Fuhrer, S. Kajigaya, A. J. Barrett, and N. S. Young Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor PNAS, September 26, 2006; 103(39): 14483 - 14488. [Abstract] [Full Text] [PDF] A. M. Healy, E. Izmailova, M. Fitzgerald, R. Walker, M. Hattersley, M. Silva, E. Siebert, J. Terkelsen, D. Picarella, M. D. Pickard, et al. PKC-{theta}-Deficient Mice Are Protected from Th1-Dependent Antigen-Induced Arthritis J. Immunol., August 1, 2006; 177(3): 1886 - 1893. [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]

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