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