CMV infections and CMV reactivations belong to the most common viral complications after kidney transplantation and can lead to severe morbidity by generalized CMV disease and to impairment of graft function [
1]. The risk assessment for CMV-associated complications is made according to the pre-transplant CMV serostatus of recipient and donor. For pediatric kidney transplantation, the international consensus guidelines recommend the use of antiviral prophylaxis with (val-)ganciclovir for 3–6 months in the case of a seropositive donor and/or seropositive recipient; in seropositive recipients, pre-emptive therapy is considered as an alternative [
26], but this medication has severe side effects such as neutropenia and nephrotoxicity [
27]. However, CMV serology and DNA load are insufficient to predict the individual course of CMV DNAemia and the risk of CMV-associated complications. CMV-specific T cells control virus replication and preliminary studies have already found that the risk of post-transplant CMV-induced disease correlated with the individual number of CMV-specific T cells. Reduced frequencies of CMV-specific T cells in transplant recipients are associated with increased incidence of infectious complications [
14,
28‐
30]. It was proven that after adult kidney transplantation, symptomatic CMV reactivations are preceded by a decrease in CMV-specific CD4 T cells frequencies and an increase in CMV load [
30]. Gamadia et al. determined the kinetics and characteristics of CMV-specific T cells in the course of primary CMV infections in adult renal transplant recipients. In asymptomatic individuals, the CMV-specific CD4 T cells response preceded CMV-specific CD8 T cells response, whereas in symptomatic individuals, the CMV-specific effector memory CD4 T cell response was delayed and only detectable after antiviral therapy [
31,
32]. The number of CMV-specific T cells before and after transplantation correlated with the risk of post-transplant CMV-associated events and DNAemia [
33,
34]. This was also true for patients receiving anti-thymocyte globulin induction therapy [
35]. Interestingly, in patients treated with the mammalian target of rapamycin (mTOR) inhibitor everolimus, the CMV-specific T cell response was more robust as compared with standard immunosuppression [
36]. In immunocompetent individuals, CMV-specific T cells are induced at onset of primary infection and persist lifelong, whereas those without CMV infection do not show any specific cellular immunity. Usually, CMV-specific T cells correlate well with CMV serology [
37], but in the case of unclear CMV-serostatus, analysis of CMV-specific T cells provides a reliable alternative to determine the pre-transplant CMV infection status, especially in patients with passive humoral immunity after infusions of plasma preparations [
38], or in infants with passive maternal antibodies [
39]. The pre-transplant absence of CMV-specific T cells in CMV-IgG-positive patients identifies CMV-naive patients at risk of post-transplant CMV-associated complications. Recently, the reverse situation was also reported, meaning that some CMV-IgG-negative kidney recipients showed pre-transplant detection of CMV-specific T cells associated with post-transplant protection from CMV infection [
8,
40,
41]. Accordingly, monitoring of CMV-specific T cells offers a superior, more reliable risk assessment of post-transplant CMV complications compared with CMV serostatus alone. In a first interventional trial using the QuantiFERON CMV assay, it was proven that CMV-specific cell-mediated immunity can be used to steer the length of antiviral therapy in the case of CMV viremia after solid organ transplantation [
42].
Especially in pediatric kidney recipients, who have a significantly higher rate of CMV negativity at time of transplantation and thereby a higher risk of post-transplant primary CMV infection, pre- and post-transplant monitoring of CMV-specific T cells might become a diagnostic tool to optimize the post-transplant management of antiviral prophylaxis and therapy. However, pediatric data concerning CMV-specific T cell monitoring after solid organ transplantation are rare. Our own observational study of pediatric kidney recipients showed that symptomatic courses of CMV infections and reactivations were found in the case of low CMV-specific CD4 T cell levels, whereas children with high virus-specific CD4 T cells showed asymptomatic courses. Until now, pediatric data has only been available in abstract form. Analysis of CMV-specific CD4 T cells might help to identify patients at risk of symptomatic CMV infections/reactivations and to decide upon necessity for and duration of antiviral prophylaxis and therapy. Hence, pre- and post-transplant monitoring of CMV-specific CD4 T cells may personalize CMV management and avoid unnecessary antiviral medication in CMV-IgG-positive children with sufficient levels of CMV-specific T cells. Further studies guiding CMV prophylaxis and therapy in children using virus-specific T cells are eagerly awaited.