A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy.
A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy.
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DOI：
10.1038/srep25852
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发表时间：
2016-05-16
影响因子：
4.6
通讯作者：
Simpson RJ
中科院分区：
文献类型：
--
作者：
Spielmann G;Bollard CM;Kunz H;Hanley PJ;Simpson RJ
巨细胞病毒（CMV）和EB病毒（EBV）感染仍然是异基因造血干细胞移植（HSCT）后发病和死亡的主要原因。供体来源的病毒特异性细胞毒性 T 细胞 (VST) 的过继转移是 HSCT 后控制 CMV 和 EBV 感染的有效治疗方法；然而，需要新的实用方法来增强来自健康捐赠者的多 VST 的离体生产。这项研究调查了单次运动对体外制造多 VST 的影响。在 30 分钟的自行车运动之前 (PRE) 和之后 (POST)，从健康的 CMV/EBV 血清阳性参与者中分离出 PBMC，并用 CMV（pp65 和 IE1）和 EBV（LMP2A 和 BMLF1）肽进行刺激，并在 8 天内进行扩增。在 VST 扩展的 POST 中，CMV pp65 (2.6)、EBV LMP2A (2.5) 和 EBV BMLF1 (4.4) 特异性 T 细胞的数量（与 PRE 的倍数差异）更大。 VST 扩增的 PRE 和 POST 具有相似的表型特征，并且同样具有 MHC 限制性杀伤自体靶细胞的能力。我们的结论是，单次运动可以增强健康供体的多 VST 的生产，而不改变其表型或功能，并且可以作为一种简单且经济的佐剂来促进同种异体过继转移免疫治疗的多 VST 的生产。
Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy.