Publikation: Cyclosporin A effects during primary and secondary activation of human umbilical cord blood T lymphocytes
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Objective: Cyclosporin A (CsA), effective in prophylaxis and treatment of graft-vs-host disease (GVHD) after human allogeneic transplantation, blunts T-cell responses by inhibiting nuclear factor of activated T cells 1 (NFAT1) activation. This laboratory has shown that NFAT1 protein expression is severely reduced in human UCB (umbilical cord blood) T cells. Since UCB is increasingly used as a hematopoietic stem cell source in allogeneic transplantation, it is important to determine whether CsA sensitivity in UCB differs from that of adult T cells.
Methods: Surface flow cytometric analysis, intracellular cytokine staining, flow cytometric analysis of cell death, and thymidine incorporation were used in this study to determine T-cell activation and effector functions during primary and secondary stimulation in the presence of CsA.
Results: Although we observed differential CsA sensitivity of T-cell activation marker (CD69, CD45RO, CD25) upregulation comparing UCB and adult, we did not observe any significant difference in CsA sensitivity of T-cell effector functions. Importantly, we observed reduced IFN-γ and TNF-α expression in UCB T cells both in primary and secondary stimulation, as well as increased rates of activation-induced cell death (AICD).
Conclusion: Thus, our studies do not support the previous hypothesis that reduced GVHD observed after UCB transplantation is attributable to increased CsA sensitivity of UCB T cells. Rather, reduced UCB T-cell cytokine production and increased AICD may be important cellular mechanisms underlying these favorable rates of GVHD in UCB transplant recipients.
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KADEREIT, Suzanne, Margaret M. KOZIK, Gwendolyn R. JUNGE, Robin E. MILLER, Laura F. SLIVKA, Linda S. BOS, Kathleen DAUM-WOODS, R. Michael SRAMKOSKI, James W. JACOBBERGER, Mary J. LAUGHLIN, 2001. Cyclosporin A effects during primary and secondary activation of human umbilical cord blood T lymphocytes. In: Experimental Hematology. 2001, 29(7), pp. 903-909. ISSN 0301-472X. Available under: doi: 10.1016/S0301-472X(01)00662-2BibTex
@article{Kadereit2001Cyclo-8168, year={2001}, doi={10.1016/S0301-472X(01)00662-2}, title={Cyclosporin A effects during primary and secondary activation of human umbilical cord blood T lymphocytes}, number={7}, volume={29}, issn={0301-472X}, journal={Experimental Hematology}, pages={903--909}, author={Kadereit, Suzanne and Kozik, Margaret M. and Junge, Gwendolyn R. and Miller, Robin E. and Slivka, Laura F. and Bos, Linda S. and Daum-Woods, Kathleen and Sramkoski, R. Michael and Jacobberger, James W. and Laughlin, Mary J.} }
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