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. |
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| 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 |
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