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在没有巨细胞病毒疾病的情况下,实体器官移植后巨细胞病毒反应性CD8 T细胞会扩增。

Cytomegalovirus-Responsive CD8 T Cells Expand After Solid Organ Transplantation in the Absence of CMV Disease.

作者信息

Higdon L E, Trofe-Clark J, Liu S, Margulies K B, Sahoo M K, Blumberg E, Pinsky B A, Maltzman J S

机构信息

Department of Medicine/Nephrology, Stanford University, Palo Alto, CA.

Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, PA.

出版信息

Am J Transplant. 2017 Aug;17(8):2045-2054. doi: 10.1111/ajt.14227. Epub 2017 Mar 13.

DOI:10.1111/ajt.14227
PMID:28199780
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5519416/
Abstract

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in solid organ transplant recipients. Approximately 60% of adults are CMV seropositive, indicating previous exposure. Following resolution of the primary infection, CMV remains in a latent state. Reactivation is controlled by memory T cells in healthy individuals; transplant recipients have reduced memory T cell function due to chronic immunosuppressive therapies. In this study, CD8 T cell responses to CMV polypeptides immediate-early-1 and pp65 were analyzed in 16 CMV-seropositive kidney and heart transplant recipients longitudinally pretransplantation and posttransplantation. All patients received standard of care maintenance immunosuppression, antiviral prophylaxis, and CMV viral load monitoring, with approximately half receiving T cell-depleting induction therapy. The frequency of CMV-responsive CD8 T cells, defined by the production of effector molecules in response to CMV peptides, increased during the course of 1 year posttransplantation. The increase commenced after the completion of antiviral prophylaxis, and these T cells tended to be terminally differentiated effector cells. Based on this small cohort, these data suggest that even in the absence of disease, antigenic exposure may continually shape the CMV-responsive T cell population posttransplantation.

摘要

巨细胞病毒(CMV)是实体器官移植受者发病和死亡的主要原因。大约60%的成年人CMV血清学呈阳性,表明既往曾接触过该病毒。初次感染消退后,CMV处于潜伏状态。在健康个体中,病毒再激活由记忆T细胞控制;由于长期免疫抑制治疗,移植受者的记忆T细胞功能降低。在本研究中,对16名CMV血清学阳性的肾移植和心脏移植受者在移植前和移植后的纵向过程中,分析了CD8 T细胞对CMV多肽即刻早期蛋白1和pp65的反应。所有患者均接受标准的维持性免疫抑制治疗、抗病毒预防和CMV病毒载量监测,约一半患者接受了耗竭T细胞的诱导治疗。由对CMV肽产生效应分子所定义的CMV反应性CD8 T细胞频率在移植后1年的过程中增加。这种增加在抗病毒预防完成后开始,并且这些T细胞倾向于是终末分化的效应细胞。基于这个小队列,这些数据表明,即使在没有疾病的情况下,抗原暴露可能在移植后持续塑造CMV反应性T细胞群体。

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本文引用的文献

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Virtual Global Transplant Laboratory Standard Operating Procedures for Blood Collection, PBMC Isolation, and Storage.虚拟全球移植实验室血液采集、外周血单个核细胞分离及储存标准操作规程
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The Cell Biology of Cytomegalovirus: Implications for Transplantation.巨细胞病毒的细胞生物学:对移植的影响。
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Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years.70岁以上健康人群血液中的巨细胞病毒载量会显著增加。
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Virus-Specific CD8(+) T Cells Cross-Reactive to Donor-Alloantigen Are Transiently Present in the Circulation of Kidney Transplant Recipients Infected With CMV and/or EBV.病毒特异性 CD8(+) T 细胞对供体同种异体抗原具有交叉反应性,在感染 CMV 和/或 EBV 的肾移植受者的循环中短暂存在。
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Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation.预测肺移植后巨细胞病毒感染防护情况的多功能T细胞特征
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The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?人类巨细胞病毒潜伏的免疫学:新型免疫治疗策略能否清除潜伏感染?
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Homeostatic expansion as a barrier to lymphocyte depletion strategies.稳态扩增作为淋巴细胞清除策略的一个障碍。
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Evaluation of cytomegalovirus (CMV)-specific T-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients.评价巨细胞病毒(CMV)特异性 T 细胞免疫在评估非免疫抑制外科和创伤重症监护病房患者活动性 CMV 感染风险中的作用。
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