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 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.


RESULTS
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.


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.
Baudouin
Véronique
V
Department of Nephrology, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Université Denis Diderot-Paris VII, Paris, France.
Dehée
Axelle
A
Pédron-Grossetete
Béatrice
B
Ansart-Pirenne
Hélène
H
Haddad
Elie
E
Maisin
Anne
A
Loirat
Chantal
C
Sterkers
Ghislaine
G
D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000503:physiopathology* / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D016030:Kidney Transplantation; D008232:Lymphoproliferative Disorders / Q000821:virology; D008297:Male; D010641:Phenotype; D011183:Postoperative Complications; D011446:Prospective Studies; D016896:Treatment Outcome; D019562:Viral Load