Kaminski Hannah, Garrigue Isabelle, Couzi Lionel, Taton Benjamin, Bachelet Thomas, Moreau Jean-François, Déchanet-Merville Julie, Thiébaut Rodolphe, Merville Pierre
Department of Nephrology, Transplantation, and Dialysis and.
Virology and National Center of Scientific Research(CNRS), Research Unit 5234, Bordeaux, France;
J Am Soc Nephrol. 2016 Feb;27(2):637-45. doi: 10.1681/ASN.2014100985. Epub 2015 Jun 8.
Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV-specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2(neg) γδ T cells in controlling CMV infection. Here, we assessed if Vδ2(neg) γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high-risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R-) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2(neg) γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2(neg) γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2(neg) γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2(neg) γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral-resistant mutant CMV strains was associated with delayed Vδ2(neg) γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2(neg) γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.
实体器官移植中的巨细胞病毒（CMV）感染与发病率和死亡率增加相关，特别是如果出现具有抗病毒抗性的CMV突变株。监测CMV特异性T细胞反应可为患者护理提供相关信息。我们和其他人已经证明Vδ2阴性γδT细胞参与控制CMV感染。在这里，我们评估了肾移植高危受者外周血中Vδ2阴性γδT细胞动力学是否可预测CMV感染的消退以及突变株的出现，这些受者包括168名接受来自血清阳性供体器官的血清阴性受者（D+R-）和104名接受抗胸腺细胞球蛋白的血清阳性受者（R+/ATG）。在2003年至2011年间移植的患者中连续测定Vδ2阴性γδT细胞百分比。监测每个感染患者中Vδ2阴性γδT细胞的生长阶段，并通过线性混合模型单独估计该阶段的扩增率。每天>0.06%的Vδ2阴性γδT细胞扩增率可预测生长阶段。感染后每天出现0.06%扩增率的时间与CMV病毒血症的消退相关（r=0.91；P<0.001）。在抗病毒治疗49天时，Vδ2阴性γδT细胞扩增开始与恢复相关，而无扩增与疾病复发和病毒血症相关。抗病毒抗性突变CMV株的出现与Vδ2阴性γδT细胞扩增延迟相关（P<0.001）。总之，对肾移植受者进行Vδ2阴性γδT细胞的纵向监测可能预测CMV感染的消退和抗病毒药物耐药性。
