The Impact of EBV Load on T-Cell Immunity in Pediatric Thoracic Transplant Recipients

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Abstract
Immunologic monitoring of pediatric transplant (Tx) recipients, who are at increased risk of Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disease, is an important goal in clinical transplantation. Here, we investigated the impact of EBV load on T-cell immunity from pediatric Tx recipients, using clinically applicable tests for improved assessment of T-cell immune competence. Thirty-five asymptomatic pediatric thoracic Tx patients were categorized into three groups according to their EBV load levels as follows: undetectable viral load (UVL), chronic low viral load (LVL) and chronic high viral load (HVL). Global and EBV-specific T-cell immunity were assessed by ATP release using Cylex Immuknow and T Cell Memory™ assays. UVL patients exhibited normal ATP release to Concanavalin A (ConA) and phytohemagglutinin (PHA; 190±86 ng/mL, 328±163 ng/mL) and detectable EBV-specific (37±34 ng/mL) ATP responses. LVL patients displayed significantly stronger responses to ConA (373±174 ng/mL), PHA (498±196 ng/mL) and EBV (152±179 ng/mL), when compared with UVL or to HVL patients (ConA 185±114 ng/mL, PHA 318±173 ng/mL, and EBV 33±42 ng/mL). Moreover, HVL patients displayed significant inverse correlation between CD4+ T-cell ATP levels and EBV loads. Evaluation of global and EBV-specific T-cell immunity provides a rapid assessment of patients’ immune competence. It is still unclear whether selective oversuppressed ATP release by CD4+ T cells reflects HVL patients at risk of posttransplant lymphoproliferative disease. Further longitudinal studies will determine the importance of Immuknow test in identifying asymptomatic HVL patients vulnerable to EBV complications.