Reduced NFAT1 Protein Expression in Human Umbilical Cord Blood T Lymphocytes

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Kadereit_et_al_1999.pdf
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1999
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Mohammad, Shaden F.
Miller, Robin E.
Daum-Woods, Kathleen
Listrom, Chad D.
McKinnon, Karen
Alali, Alborz
Bos, Linda S.
Iacobucci, Michelle L.
Sramkoski, R. Michael
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Blood. 1999, 94(9), pp. 3101-3107
Zusammenfassung

Umbilical cord blood (UCB) stem cells from related and unrelated allogeneic donors have emerged as novel treatment for patients with hematologic malignancies. The incidence and severity of acute graft-versus-host disease (GVHD) after UCB transplantation compares favorably with that observed in recipients of matched unrelated donor allogeneic grafts, but remains a major cause of morbidity and mortality. It has been shown that stimulated lymphocytes from UCB have reduced production of cytokines including interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which play a role in GVHD pathophysiology.We investigated the molecular mechanisms underlying this reduced cytokine production by analyzing expression of nuclear factor of activated T cells-1 (NFAT1) in UCB T cells. We detected no constitutive expression of NFAT1 protein in unstimulated UCB T cells compared with adult T cells. Moreover, although NFAT1 expression in UCB T cells was upregulated after prolonged (40 hours) T-cell stimulation, it was only partially upregulated when compared with adult controls. Our observation of minimal NFAT1 xpression after stimulation correlated with reduced cytoplasmic IFN-γ and TNF-α roduction in UCB T cells studied simultaneously. Reduced NFAT1 expression may blunt amplification of donor UCB T-cell alloresponsiveness against recipient antigens, thereby potentially limiting GVHD incidence and severity after allogeneic UCB transplantation.

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570 Biowissenschaften, Biologie
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ISO 690KADEREIT, Suzanne, Shaden F. MOHAMMAD, Robin E. MILLER, Kathleen DAUM-WOODS, Chad D. LISTROM, Karen MCKINNON, Alborz ALALI, Linda S. BOS, Michelle L. IACOBUCCI, R. Michael SRAMKOSKI, James W. JACOBBERGER, Mary J. LAUGHLIN, 1999. Reduced NFAT1 Protein Expression in Human Umbilical Cord Blood T Lymphocytes. In: Blood. 1999, 94(9), pp. 3101-3107
BibTex
@article{Kadereit1999Reduc-7766,
  year={1999},
  title={Reduced NFAT1 Protein Expression in Human Umbilical Cord Blood T Lymphocytes},
  number={9},
  volume={94},
  journal={Blood},
  pages={3101--3107},
  author={Kadereit, Suzanne and Mohammad, Shaden F. and Miller, Robin E. and Daum-Woods, Kathleen and Listrom, Chad D. and McKinnon, Karen and Alali, Alborz and Bos, Linda S. and Iacobucci, Michelle L. and Sramkoski, R. Michael and Jacobberger, James W. and Laughlin, Mary J.}
}
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    <dcterms:abstract xml:lang="eng">Umbilical cord blood (UCB) stem cells from related and unrelated allogeneic donors have emerged as novel treatment for patients with hematologic malignancies. The incidence and severity of acute graft-versus-host disease (GVHD) after UCB transplantation compares favorably with that observed in recipients of matched unrelated donor allogeneic grafts, but remains a major cause of morbidity and mortality. It has been shown that stimulated lymphocytes from UCB have reduced production of cytokines including interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which play a role in GVHD pathophysiology.We investigated the molecular mechanisms underlying this reduced cytokine production by analyzing expression of nuclear factor of activated T cells-1 (NFAT1) in UCB T cells. We detected no constitutive expression of NFAT1 protein in unstimulated UCB T cells compared with adult T cells. Moreover, although NFAT1 expression in UCB T cells was upregulated after prolonged (40 hours) T-cell stimulation, it was only partially upregulated when compared with adult controls. Our observation of minimal NFAT1 xpression after stimulation correlated with reduced cytoplasmic IFN-γ and TNF-α  roduction in UCB T cells studied simultaneously. Reduced NFAT1 expression may blunt amplification of donor UCB T-cell alloresponsiveness against recipient antigens, thereby potentially limiting GVHD incidence and severity after allogeneic UCB transplantation.</dcterms:abstract>
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