Relationship between CD8+ T-cell phenotype and function, Epstein-Barr virus load, and clinical outcome in pediatric renal transplant recipients: a prospective study

• Published in: Transplantation Vol. 77; no. 11; p. 1706
• Main Authors: Baudouin, Véronique, Dehée, Axelle, Pédron-Grossetete, Béatrice, Ansart-Pirenne, Hélène, Haddad, Elie, Maisin, Anne, Loirat, Chantal, Sterkers, Ghislaine
• Format: Journal Article
• Language: English
• Published: United States 15.06.2004
• Subjects: Adolescent; CD8-Positive T-Lymphocytes; Child; Child, Preschool; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - physiopathology; Epstein-Barr Virus Infections - virology; Female; Herpesvirus 4, Human - isolation & purification; Humans; Infant; Kidney Transplantation; Lymphoproliferative Disorders - virology; Male; Phenotype; Postoperative Complications; Prospective Studies; Treatment Outcome; Viral Load
• ISSN: 0041-1337
• DOI: 10.1097/01.TP.0000131168.21930.5C

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). Twenty-two patients were enrolled at the time of Tx and three at diagnosis of EBV-induced post-transplant 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. For three children with post-Tx uncomplicated primary EBV infection, EBV load peaked by months 1 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. 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.