Reduced NFAT1 protein expression in human umbilical cord blood T lymphocytes

Umbilical cord blood (UCB) stem cells from related and unrelated allogeneic donors have emerged as novel treatment for patients with hematologic malig nancies. The incidence and severity of acute graft-versus-host disease (GVH D) after UCB transplantation compares favorably with that observed in recip ients of matched unrelated donor allogeneic grafts, but remains a major cau se of morbidity and mortality. It has been shown that stimulated lymphocyte s from UCB have reduced production of cytokines including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which play a role in GVHD pathophysiology. We investigated the molecular mechanisms underlyin g this reduced cytokine production by analyzing expression of nuclear facto r of activated T cells-1 (NFAT1) in UCB T cells. We detected no constitutiv e expression of NFAT1 protein in unstimulated UCB T cells compared with adu lt T cells. Moreover, although NFAT1 expression in UCB T cells was upregula ted after prolonged (40 hours) T-cell stimulation, it was only partially up regulated when compared with adult controls. Our observation of minimal NFA T1 expression after stimulation correlated with reduced cytoplasmic IFN-gam ma and TNF-alpha production in UCB T cells studied simultaneously. Reduced NFAT1 expression may blunt amplification of donor UCB T-cell alloresponsive ness against recipient antigens, thereby potentially limiting GVHD incidenc e and severity after allogeneic UCB transplantation. (C) 1999 by The Americ an Society of Hematology.