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维生素C增强抗病毒T细胞反应,为改进过继性免疫疗法中病毒特异性T细胞的制备提供了新策略。

Enhancement of Antiviral T-Cell Responses by Vitamin C Suggests New Strategies to Improve Manufacturing of Virus-Specific T Cells for Adoptive Immunotherapy.

作者信息

Laubert Miriam, Bonifacius Agnes, Dragon Anna Christina, Mangare Caroline, Blasczyk Rainer, Huehn Jochen, Eiz-Vesper Britta

机构信息

Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, 30625 Hannover, Germany.

Department Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.

出版信息

Biology (Basel). 2022 Mar 30;11(4):536. doi: 10.3390/biology11040536.

DOI:10.3390/biology11040536
PMID:35453735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9032103/
Abstract

Allogeneic and autologous transplantation of hematopoietic stem cells (HSCT) are being routinely used to treat patients with leukemia and lymphoma. Due to the required immunosuppression after stem cell transplantation, infection and reactivation by viruses are life-threatening complications. In recent years, adoptive transfer using virus-specific T cells (VSTs) has emerged as alternative to conventional therapies. Since vitamins are described to influence the immune system and its cellular components, the aim of this study was to examine whether vitamins modulate VST function and thereby enable an improvement of therapy. For that, we investigated the impact of vitamin C and D on the functionality of cytomegalovirus (CMV)-specific T cells isolated from CMV-seropositive healthy donors. We were able to show that vitamin C increases the expansion and activation state of CMV-specific T cells, and an increased influence of vitamin C was observed on cells isolated from male donors and donors above 40 years of age. A higher frequency of the terminally differentiated effector memory CD8 T-cell population in these donors indicates a connection between these cells and the enhanced response to vitamin C. Thus, here we provide insights into the impact of vitamin C on cytotoxic T cells as well as possible additional selection criteria and strategies to improve VST functionality.

摘要

造血干细胞的异体和自体移植(HSCT)正被常规用于治疗白血病和淋巴瘤患者。由于干细胞移植后需要免疫抑制,病毒感染和再激活是危及生命的并发症。近年来,使用病毒特异性T细胞(VST)的过继性转移已成为传统疗法的替代方法。由于维生素被描述为会影响免疫系统及其细胞成分,本研究的目的是检查维生素是否能调节VST功能,从而改善治疗效果。为此,我们研究了维生素C和D对从巨细胞病毒(CMV)血清阳性健康供体中分离出的CMV特异性T细胞功能的影响。我们能够证明维生素C可增加CMV特异性T细胞的扩增和激活状态,并且在从男性供体和40岁以上供体中分离出的细胞上观察到维生素C的影响增强。这些供体中终末分化的效应记忆CD8 T细胞群体的频率较高,表明这些细胞与对维生素C的增强反应之间存在联系。因此,我们在此提供了关于维生素C对细胞毒性T细胞的影响以及改善VST功能的可能的附加选择标准和策略的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/39df5c89ef0a/biology-11-00536-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/452e222092c2/biology-11-00536-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/7de924ba8a81/biology-11-00536-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/015ca009484d/biology-11-00536-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/b55fa40351cb/biology-11-00536-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/afe28a2b3268/biology-11-00536-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/39df5c89ef0a/biology-11-00536-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/452e222092c2/biology-11-00536-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/7de924ba8a81/biology-11-00536-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/015ca009484d/biology-11-00536-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/b55fa40351cb/biology-11-00536-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/afe28a2b3268/biology-11-00536-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e3/9032103/39df5c89ef0a/biology-11-00536-g006.jpg

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