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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4608-4617. Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-05-1732. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1732v1 102/13/4608    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 Kaminski, B. A. Articles by Laughlin, M. J. Search for Related Content PubMed PubMed Citation Articles by Kaminski, B. A. Articles by Laughlin, M. J. Related Collections Transplantation Genomics Chemokines, Cytokines, and Interleukins Gene Therapy Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Reduced expression of NFAT-associated genes in UCB versus adult CD4+ T lymphocytes during primary stimulation Beth A. Kaminski, Suzanne Kadereit, Robin E. Miller, Patrick Leahy, Kevin R. Stein, David A. Topa, Tomas Radivoyevitch, Martina L. Veigl, and Mary J. Laughlin From the Department of Medicine, Ireland Cancer Center, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH. The cellular and molecular mechanisms underlying the blunted allo-responsiveness of umbilical cord blood (UCB) T cells have not been fully elucidated. Protein expression of NFATc2 (nuclear factor of activated T cells c2), a critical transcription factor necessary for up-regulation of multiple cytokines known to amplify T-cell allogeneic responses, is reduced in UCB T cells. Affymetrix oligonucleotide microarrays were used to compare gene expression of primary purified CD4+ UCB T cells to adult peripheral blood CD4+ T cells (AB) at baseline, 6, and 16 hours of primary stimulation. NFAT-regulated genes exhibited lower expression in UCB CD4+ T cells including the following: granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon- (IFN-), tumor necrosis factor- (TNF-), interleukin 3 (IL-3), IL-4, IL-5, IL-13, IL-2 receptor (IL-2R; CD25), CD40L, and macrophage inflammatory protein 1 (MIP-1). Transcription factors involved in the NFAT pathway including C/EBP, JunB, and Fosl1 (Fra-1), as well as Th1- and Th2-related transcription factors STAT4 (signal transducers and activators of transcription 4), T-bet, and c-maf showed reduced expression in UCB compared with AB during primary stimulation. Reduced cytokine, chemokine, and receptor expression was also found in UCB. Gene array data were confirmed using RNase protection assays, flow cytometry, and quantitative multiplexed cytokine measurements. Reduced global expression of NFAT-associated genes, as well as cytokines and chemokines, in UCB CD4+ T cells may contribute to the decreased graft-versus-host disease (GVHD) observed after UCB transplantation. (Blood. 2003;102:4608-4617) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Ito, K. J. Ishii, M. Gursel, H. Shirotra, A. Ihata, and D. M. Klinman CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection J. Immunol., January 15, 2005; 174(2): 777 - 782. [Abstract] [Full Text] [PDF] W. R. Godfrey, D. J. Spoden, Y. G. Ge, S. R. Baker, B. Liu, B. L. Levine, C. H. June, B. R. Blazar, and S. B. Porter Cord blood CD4+CD25+-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function Blood, January 15, 2005; 105(2): 750 - 758. [Abstract] [Full Text] [PDF] H. Jiang, C. Van de Ven, P. Satwani, L. V. Baxi, and M. S. Cairo Differential Gene Expression Patterns by Oligonucleotide Microarray of Basal versus Lipopolysaccharide-Activated Monocytes from Cord Blood versus Adult Peripheral Blood J. Immunol., May 15, 2004; 172(10): 5870 - 5879. [Abstract] [Full Text] [PDF]

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