Serological identification of the cytomegalovirus (CMV) status in children less than 18 months of age is complicated by the variable persistence of maternal antibodies. As T cells are not passively transferred, we attempted to assess whether CMV-specific cellular immunity may be superior to determine the actual CMV status; we also performed a functional characterization of T-cell immunity in childhood. Antibodies from 59 mothers and 168 children were determined, and specific CD4 + T cells were identified by induction of IFN-γ, IL-2, TNF-α, IL-4, and IL-17 after CMV-specific and polyclonal stimulation. Agreement between both tests was perfect for mothers and children more than 18 months. Among infants less than 18 months, 17/30 were concordantly negative. Interestingly, 8/13 seropositive children had detectable CMV-specific T cells, whereas only 5/13 were T-cell negative, indicating passive immunity. CMV-specific T cells from young infants differed in cytokine profiles from that of older age groups, and polyclonal effector T-cell frequencies were higher in young infants with detectable CMV-specific T cells compared with those without. In conclusion, the majority of young infants with CMV-specific antibodies show evidence of true infection, which indicates that passive immunity is overestimated. Our data may have important implications for improved risk stratification and CMV management in infants in the setting of transplantation. Keywords IntroductionComplications related to cytomegalovirus (CMV) are among the most serious infectious complications after organ transplantation Correspondence: Prof. Martina Sester e-mail: martina.sester@uks.eu in both adults and children [1][2][3]. The risk for CMV infection and disease largely depends on the CMV status of the donor and the recipient, which is determined prior to transplantation based on CMV serology. While the determination of CMV-specific humoral * These authors contributed equally to this work. Eur. J. Immunol. 2013. 43: 1099-1108 immunity is a reliable and widely used method to determine evidence of prior infection, it has limitations in clinical situations where passive antibodies may exist due to transfusion of plasma products or due to natural existence of maternal antibodies in young infants. This raises uncertainty as to the correct assignment of the CMV status in recipients or donors after plasma transfusion or in children below the age of 18 months. Based on this uncertainty, current guidelines recommend that the highest risk should be assumed for any transplant arrangement where passive antibody titers may exist in either the donor or the recipient, i.e. the recipient should always be assumed as CMV-negative and the donor should be considered as CMVpositive [1,2]. Based on this clinical dilemma, the development of alternative approaches to assess the actual infection status was recently defined as an important research priority to improve posttransplant management in children [1].We have previously shown in adults that the determination of CMV-specifi...

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Cell-mediated immunity assays could be valuable for risk assessment of organ donors, but no data exist on their feasibility in deceased donors. In this study, 105 deceased donors (52.3 AE 16.9 years) were screened at the time of organ procurement. Pathogen-specific stimulation was performed using a cytomegalovirus (CMV) lysate, tuberculin (purified protein derivative [PPD]) and soluble Mycobacterium tuberculosis-specific ESAT-6/CFP-10 proteins in combination with an inhouse fluorescence-activated cell sorting (FACS) assay or commercial assay formats (QuantiFERON-CMV/TB for ELISA, T-SPOT.TB for ELISPOT). CMV-IgG antibody titers were determined as gold standard for CMV infection; 51.4% of samples were CMV seropositive. Indeterminate results were observed in 47.6% of ELISA, 12.5% of FACS and 0% of ELISPOT assays. Agreement with serology was highest for FACS (95.6%, k ¼ 0.91), followed by ELISPOT (84.0%, k ¼ 0.68) and ELISA (80.0%, k ¼ 0.60). Agreement between ELISA and serology increased if the CMV lysate was used as stimulus (96.7%, k ¼ 0.92). Among the T cell assays, agreement between ELISPOT and FACS was highest (k ¼ 0.70). PPDpositive results among valid samples differed between assays (26.5% for ELISA, 23.1% for FACS and 50.5% for ELISPOT); 2.0% were QuantiFERON-TB positive, 3.3% were ESAT-6/CFP-10-positive in FACS and 13.4% were positive in the T-SPOT.TB assay. In conclusion, cellular immunity may be analyzed from samples of deceased donors, although the assays differ in the rate of positivity and indeterminate results.

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