Higdon L E, Trofe-Clark J, Liu S, Margulies K B, Sahoo M K, Blumberg E, Pinsky B A, Maltzman J S
Department of Medicine/Nephrology, Stanford University, Palo Alto, CA.
Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, PA.
Am J Transplant. 2017 Aug;17(8):2045-2054. doi: 10.1111/ajt.14227. Epub 2017 Mar 13.
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.
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。