title: Reduced NFAT1 protein expression in human umbilical cord blood T lymphocytes.
abstract: 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-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), 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-gamma and TNF-alpha 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.
authors.affiliation: University Hospitals Ireland Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106-5065, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kadereit
authors.forename: S F
authors.initials: SF
authors.lastname: Mohammad
authors.forename: R E
authors.initials: RE
authors.lastname: Miller
authors.forename: K D
authors.initials: KD
authors.lastname: Woods
authors.forename: C D
authors.initials: CD
authors.lastname: Listrom
authors.forename: K
authors.initials: K
authors.lastname: McKinnon
authors.forename: A
authors.initials: A
authors.lastname: Alali
authors.forename: L S
authors.initials: LS
authors.lastname: Bos
authors.forename: M L
authors.initials: ML
authors.lastname: Iacobucci
authors.forename: M R
authors.initials: MR
authors.lastname: Sramkoski
authors.forename: J W
authors.initials: JW
authors.lastname: Jacobberger
authors.forename: M J
authors.initials: MJ
authors.lastname: Laughlin
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005312:Fetal Blood; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors