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Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 3101-3107
Reduced NFAT1 Protein Expression in Human Umbilical Cord Blood T
Lymphocytes
Suzanne Kadereit,
Shaden F. Mohammad,
Robin E. Miller,
Kathleen
Daum Woods,
Chad D. Listrom,
Karen McKinnon,
Alborz Alali,
Linda S. Bos,
Michelle L. Iacobucci,
Michael R. Sramkoski,
James W. Jacobberger, and
Mary J. Laughlin
From the University Hospitals Ireland Comprehensive Cancer Center,
Case Western Reserve University, Cleveland, OH; and the Lineberger
Comprehensive Cancer Center, University of North Carolina at Chapel
Hill, Chapel Hill, NC.
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- (IFN-) and
tumor necrosis factor- (TNF-), 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 expression after stimulation
correlated with reduced cytoplasmic IFN- and TNF- production 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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