Reduced NFAT1 Protein Expression in Human Umbilical Cord Blood T Lymphocytes

Autor: Kadereit, Suzanne, 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, Jacobberger, James W., Laughlin, Mary J.
Rok vydání: 1999
Předmět:
Zdroj: Blood. 94:3101-3107
ISSN: 1528-0020
0006-4971
Popis: 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- (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-γ 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.
Databáze: OpenAIRE