Relationship between Cd8+ T-cell phenotype and function, Epstein-Barr virus load, and clinical outcome in pediatric renal transplant recipients:: A prospective study

Background. The authors studied the relationship between the dynamics of Epstein-Barr virus (EBV) load, CD8(+) T-cell activation and differentiation, and EBV-associated symptoms in 25 children after kidney transplantation (Tx). Methods. Twenty-two patients were enrolled at the time of Tx and three at diagnosis of EBV-induced posttransplant lymphoproliferative disease (PTLD). EBV load was serially measured by a semiquantitative method of DNA amplification in blood cells. The percentages of activated (human leukocyte antigen-DR+) and of effector-memory (CD28(-)) CD8(+) circulating cytolytic T lymphocytes (CTL) were serially evaluated by flow cytometry. The cytotoxic potential of CTL was assessed by a CD3-redirected cytotoxic assay. Results. For three children with post-Tx uncomplicated primary EBV infection, EBV load peaked by months I to 2 after Tx and declined spontaneously by months 3 to 6, whereas expansion of activated and effector-memory CTL was absent (one case) or transient and moderate (two cases). In 15 patients who were EBV-seropositive before Tx and who did not develop EBV-PTLD, transient elevation of EBV load but no noticeable changes in CTL phenotype were observed. In contrast, in one child who was also EBV-seropositive before Tx but who developed EBV-PTLD, a major and sustained elevation of EBV load and of activated and effector-memory CTL was observed. In three patients retrospectively enrolled at diagnosis of EBV-PTLD, sustained elevation of both viral load and activated T cells was also noticed. Finally, increased cytotoxic activity correlated with increased level of activated CTL. Conclusions. An association between high and sustained T-cell activation, EBV load, and the occurrence of EBV-PTLD was observed. Furthermore, intense cytotoxic activity was observed in EBV-PTLD, with favorable outcome.