Redondo-Pachón Dolores, Crespo Marta, Yélamos Jose, Muntasell Aura, Pérez-Sáez María José, Pérez-Fernández Silvia, Vila Joan, Vilches Carlos, Pascual Julio, López-Botet Miguel
Servei de Nefrologia, Hospital del Mar, Barcelona 08003, Spain.
Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona 08003, Spain.
J Immunol. 2017 Jan 1;198(1):94-101. doi: 10.4049/jimmunol.1601236. Epub 2016 Dec 2.
CMV infection in kidney transplant recipients (KTRs) has been associated with an increased risk for graft loss and reduced host survival. CMV promotes persistent expansions of NK cells expressing the CD94/NKG2C receptor. The NKG2C (KLRC2) gene is frequently deleted, and copy number influences the adaptive response of NKG2C NK cells. The distribution of NKG2C NK cells and NKG2C genotypes (NKG2C, NKG2C, NKG2C) were studied in cross-sectional (n = 253) and prospective (n = 122) KTR cohorts. Assessment of CMV viremia was restricted to symptomatic cases in the retrospective study, but was regularly monitored in the prospective cohort. Overall, the proportions of NKG2C NK cells were significantly higher in KTRs who had suffered posttransplant symptomatic CMV infection in the cross-sectional study. Yet, along the prospective follow-up (3, 6, 12, and 24 mo), posttransplant NKG2C NK cell expansions were not observed in every patient with detectable viremia who received preemptive antiviral therapy, suggesting that the adaptive NK cell response may be inversely related with the degree of CMV control. Remarkably, the incidence of posttransplant viremia was reduced among cases with high pretransplant levels of NKG2C NK cells. The NKG2C genotype distribution was comparable in KTR and healthy controls, and greater proportions of NKG2C cells were detected in NKG2C than in NKG2C patients. Yet, a trend toward increased NKG2C and reduced NKG2C frequencies associated with symptomatic infection was appreciated in both cohorts. Altogether, our results indirectly support that adaptive NKG2C NK cells are involved in the control of CMV in KTRs.
肾移植受者（KTRs）中的巨细胞病毒（CMV）感染与移植肾丢失风险增加及宿主生存率降低相关。CMV可促进表达CD94/NKG2C受体的自然杀伤（NK）细胞持续扩增。NKG2C（KLRC2）基因常发生缺失，其拷贝数会影响NKG2C NK细胞的适应性反应。在横断面（n = 253）和前瞻性（n = 122）KTR队列中研究了NKG2C NK细胞的分布及NKG2C基因型（NKG2C、NKG2C、NKG2C）。在回顾性研究中，CMV病毒血症的评估仅限于有症状的病例，但在前瞻性队列中会定期进行监测。总体而言，在横断面研究中，发生移植后有症状CMV感染的KTRs中，NKG2C NK细胞的比例显著更高。然而，在前瞻性随访期间（3、6、12和24个月），在接受抢先抗病毒治疗且病毒血症可检测到的每位患者中，并未观察到移植后NKG2C NK细胞的扩增，这表明适应性NK细胞反应可能与CMV的控制程度呈负相关。值得注意的是，移植前NKG2C NK细胞水平较高的病例中，移植后病毒血症的发生率降低。KTR与健康对照的NKG2C基因型分布相当，与NKG2C患者相比，在NKG2C患者中检测到的NKG2C细胞比例更高。然而，在两个队列中均观察到与有症状感染相关的NKG2C频率增加和NKG2C频率降低的趋势。总之，我们的结果间接支持适应性NKG2C NK细胞参与KTRs中CMV的控制。
