Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center, Erasmus University Rotterdam, Rotterdam, Netherlands.
Laboratory of Translational Immunology, Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands.
Front Immunol. 2018 Mar 1;9:389. doi: 10.3389/fimmu.2018.00389. eCollection 2018.
Cytomegalovirus (CMV) infection can cause significant complications after transplantation, but recent emerging data suggest that CMV may paradoxically also exert beneficial effects in two specific allogeneic transplant settings. These potential benefits have been underappreciated and are therefore highlighted in this review. First, after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK) cell-replete grafts, CMV reactivation is associated with protection from leukemic relapse. This association was not observed for other hematologic malignancies. This anti-leukemic effect might be mediated by CMV-driven expansion of donor-derived memory-like NKG2C NK and Vδ2 T-cells. Donor-derived NK cells probably recognize recipient leukemic blasts by engagement of NKG2C with HLA-E and/or by the lack of donor (self) HLA molecules. Vδ2 T cells probably recognize as yet unidentified antigens on leukemic blasts via their TCR. Second, immunological imprints of CMV infection, such as expanded numbers of Vδ2 T cells and terminally differentiated TCRαβ T cells, as well as enhanced NKG2C gene expression in peripheral blood of operationally tolerant liver transplant patients, suggest that CMV infection or reactivation may be associated with liver graft acceptance. Mechanistically, poor alloreactivity of CMV-induced terminally differentiated TCRαβ T cells and CMV-induced IFN-driven adaptive immune resistance mechanisms in liver grafts may be involved. In conclusion, direct associations indicate that CMV reactivation may protect against AML relapse after allogeneic HSCT, and indirect associations suggest that CMV infection may promote allograft acceptance after liver transplantation. The causative mechanisms need further investigations, but are probably related to the profound and sustained imprint of CMV infection on the immune system.
巨细胞病毒 (CMV) 感染可在移植后引起严重并发症，但最近出现的新数据表明，CMV 可能在两种特定的同种异体移植环境中产生有益影响。这些潜在的益处被低估了，因此在这篇综述中重点强调。首先，在使用 T 细胞和自然杀伤 (NK) 细胞丰富的移植物进行急性髓系白血病 (AML) 的异基因造血干细胞移植 (HSCT) 后，CMV 再激活与白血病复发的保护相关。这种关联在其他血液系统恶性肿瘤中并未观察到。这种抗白血病作用可能是由 CMV 驱动的供体衍生记忆样 NKG2C NK 和 Vδ2 T 细胞的扩张介导的。供体来源的 NK 细胞可能通过 NKG2C 与 HLA-E 的结合和/或缺乏供体（自身）HLA 分子来识别受体白血病细胞。Vδ2 T 细胞可能通过其 TCR 识别白血病细胞上尚未确定的抗原。其次，CMV 感染的免疫印记，如 Vδ2 T 细胞和终末分化 TCRαβ T 细胞数量的扩增，以及手术耐受的肝移植患者外周血中 NKG2C 基因表达的增强，表明 CMV 感染或再激活可能与肝移植物接受有关。从机制上讲，CMV 诱导的终末分化 TCRαβ T 细胞和 CMV 诱导的 IFN 驱动的适应性免疫抵抗机制的低同种反应性可能涉及其中。总之，直接关联表明 CMV 再激活可能防止异基因 HSCT 后 AML 复发，间接关联表明 CMV 感染可能促进肝移植后的同种异体移植物接受。因果机制需要进一步研究，但可能与 CMV 感染对免疫系统的深刻和持续影响有关。
