Reduced expression of NFAT-associated genes in UCB versus adult CD4plus T lymphocytes during primary stimulation

Kaminski, Beth  A.; Kadereit, Suzanne; Miller, Robin E.; Leahy, Patrick; Stein, Kevin R.; Topa, David A.; Radivoyevitch, Tomas; Veigl, Martina L.; Laughlin, Mary J.

Reduced expression of NFAT-associated genes in UCB versus adult CD4plus T lymphocytes during primary stimulation

Dateien

Kaminski_et_al._2003.pdfGröße: 357.37 KBDownloads: 163

Datum

2003

Autor:innen

Kaminski, Beth A.

Kadereit, Suzanne

Miller, Robin E.

Leahy, Patrick

Stein, Kevin R.

Topa, David A.

Radivoyevitch, Tomas

Veigl, Martina L.

Laughlin, Mary J.

URI (zitierfähiger Link)

http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-123250

Link zur Lizenz

Urheberrechtlich geschützt

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Blood. 2003, 102(13), pp. 4608-4617

Zusammenfassung

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-{gamma} (IFN-{gamma}), tumor necrosis factor-{alpha} (TNF-{alpha}), interleukin 3 (IL-3), IL-4, IL-5, IL-13, IL-2 receptor {alpha} (IL-2R{alpha}; CD25), CD40L, and macrophage inflammatory protein 1 {alpha} (MIP-1{alpha}). Transcription factors involved in the NFAT pathway including C/EBP{beta}, 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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

KAMINSKI, Beth A., Suzanne KADEREIT, Robin E. MILLER, Patrick LEAHY, Kevin R. STEIN, David A. TOPA, Tomas RADIVOYEVITCH, Martina L. VEIGL, Mary J. LAUGHLIN, 2003. Reduced expression of NFAT-associated genes in UCB versus adult CD4plus T lymphocytes during primary stimulation. In: Blood. 2003, 102(13), pp. 4608-4617

BibTex

@article{Kaminski2003Reduc-8227,
  year={2003},
  title={Reduced expression of NFAT-associated genes in UCB versus adult CD4plus T lymphocytes during primary stimulation},
  number={13},
  volume={102},
  journal={Blood},
  pages={4608--4617},
  author={Kaminski, Beth  A. and Kadereit, Suzanne and Miller, Robin E. and Leahy, Patrick and Stein, Kevin R. and Topa, David A. and Radivoyevitch, Tomas and Veigl, Martina L. and Laughlin, Mary J.}
}

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    <dcterms:abstract xml:lang="eng">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-{gamma} (IFN-{gamma}), tumor necrosis factor-{alpha} (TNF-{alpha}), interleukin 3 (IL-3), IL-4, IL-5, IL-13, IL-2 receptor {alpha} (IL-2R{alpha}; CD25), CD40L, and macrophage inflammatory protein 1 {alpha} (MIP-1{alpha}). Transcription factors involved in the NFAT pathway including C/EBP{beta}, 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.</dcterms:abstract>
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