Cytomegalovirus‐specific T cells are detectable in early childhood and allow assignment of the infection status in children with passive maternal antibodies

Abstract

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...

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

“…At 24 weeks, Ͻ20% of infants had IgG of high avidity, which could represent either transplacentally acquired maternal antibody or already mature infant antibody from primary infection. Our results indicate that most maternal antibody has waned by 6 months, consistent with a study from China suggesting that the maternally acquired anti-CMV IgG in infants disappears before 8 months of age (24); similarly, a study from Germany concluded that maternal antibody against CMV decayed by 12 months (25).…”

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

“…Several methods rely on the functional analysis of T-cell-secreted cytokines or the T-cell phenotype (i.e., gamma interferon [IFN-␥], tumor necrosis factor alpha [TNF-␣], interleukin 2 [IL-2], CD107a, programmed cell death protein 1 [PD-1]) upon antigen stimulation, while other methods, such as tetramer assays, are based on the direct detection of antigen-specific T cells or cell proliferation assays (14)(15)(16)(17). Moreover, tetramer assays are limited to a few human leukocyte antigen (HLA) haplotypes and thus may not be applicable for all patients.…”

Comparative Analysis of Assays for Detection of Cell-Mediated Immunity Toward Cytomegalovirus and M. tuberculosis in Samples From Deceased Organ Donors

“…In this study, we have performed a detailed comparative analysis of the performance characteristics of three assay principles for the detection of cellular immunity toward CMV and M. tuberculosis in samples from deceased donors. Unlike latent infection with M. tuberculosis, where the assignment of the infection status is hampered by the lack of an independent gold standard for positivity, evaluation of CMV-specific T cell assays has the advantage that CMV-IgG serology may serve as a reliable gold standard for the true infection status (6,7,13) and was therefore included in our study.…”

“…When compared with humoral IgG as a gold standard for CMV infection, the presence of CMV-specific immunity was shown to closely correlate with antibody responses (6,7). Likewise, specific immunity toward M. tuberculosis is readily detectable in vitro.…”