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儿童肝移植受者病毒特异性 T 细胞免疫的动态变化。

Dynamics of virus-specific T cell immunity in pediatric liver transplant recipients.

机构信息

Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA.

Department of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.

出版信息

Am J Transplant. 2018 Sep;18(9):2238-2249. doi: 10.1111/ajt.14967. Epub 2018 Jul 10.

Abstract

Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between posttransplant immunosuppression and circulating virus-specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year posttransplant. Following transplant, there was an immediate decline in circulating virus-specific T cells, which recovered posttransplant, coincident with the introduction and subsequent routine tapering of immunosuppression. Furthermore, 12 of 14 infections/reactivations that occurred posttransplant were successfully controlled with immunosuppression reduction (and/or antiviral use) and in all cases we detected a temporal increase in the circulating frequency of virus-specific T cells directed against the infecting virus, which was absent in 2 cases where infections remained uncontrolled by the end of follow-up. Our study illustrates the dynamic changes in virus-specific T cells that occur in children following liver transplantation, driven both by active viral replication and modulation of immunosuppression.

摘要

实体器官移植(SOT)后的免疫抑制对细胞免疫有有害影响,导致频繁和长期的病毒感染。为了更好地了解移植后免疫抑制与循环病毒特异性 T 细胞之间的关系,我们前瞻性地监测了 16 名接受肝移植的儿童在移植后长达 1 年的时间内针对一系列潜伏(CMV、EBV、HHV6、BK)和裂解(AdV)病毒的 T 细胞的频率和功能。移植后,循环病毒特异性 T 细胞立即下降,在移植后恢复,与免疫抑制的引入和随后的常规逐渐减少同步。此外,移植后发生的 14 次感染/再激活中的 12 次通过减少免疫抑制(和/或使用抗病毒药物)成功得到控制,在所有情况下,我们都检测到针对感染病毒的循环病毒特异性 T 细胞的频率出现暂时增加,而在 2 例感染在随访结束时仍未得到控制的情况下则没有这种情况。我们的研究说明了儿童肝移植后病毒特异性 T 细胞的动态变化,这是由病毒的主动复制和免疫抑制的调节共同驱动的。

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Virus-specific T-cell therapy in solid organ transplantation.
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