Monitoring of Epstein-Barr virus load and killer T cells in pediatric renal transplant recipients.
OBJECTIVE
The aim of this study is to establish a monitoring method to prevent Epstein-Barr virus (EBV)-associated symptoms including post-transplant lymphoproliferative disorder (PTLD) that occur after pediatric renal transplantation.


METHODS
Circulating EBV loads were quantified by real-time PCR every 1 - 3 months after grafting in 22 pediatric recipients (13 EBV-seronegative [R(-)] and 9 EBV-seropositive [R(+)] recipients before grafting). The peripheral blood cell populations of non-specific activated killer cells (CD8+HLA-DR+ phenotype) in 13 R(-) recipients and EBV-specific cytotoxic T cells (CTLs) reactive with a tetramer expressing HLA-A24-restricted EBV-specific antigens in 8 of 13 R(-) recipients were determined by flow cytometry.


RESULTS
EBV-associated symptoms including PTLD (2 cases) were found in 4 R(-) and none of the R(+) recipients. The maximum of EBV load in the R(-) group was significantly higher that in the R(+) group. In R(-) recipients, 4 symptomatic cases had significantly more EBV genome than asymptomatic cases. EBV-specific CTLs were detected in 6 of the 8 R(-) recipients, but these CTLs could not be detected in 1 of the 2 cases at onset of PTLD. The percentage of CD8+HLA-DR+ cells was significantly higher in asymptomatic recipients than in recipients with EBV-associated symptoms whose EBV loads were over 400 copies/microg DNA.


CONCLUSIONS
Monitoring of killer T cells and EBV loads may allow assessment of the risk of EBV-associated symptoms, and high EBV loads and low EBV-specific and/or non-specific CTL responses may be predictive for development of EBV-associated symptoms such as PTLD.
Sato
T
T
Department of Pediatrics, Kochi Medical School, Kochi University, Kochi, Japan.
Fujieda
M
M
Maeda
A
A
Tanaka
E
E
Miyamura
M
M
Chikamoto
H
H
Hisano
M
M
Akioka
Y
Y
Ishiura
Y
Y
Dohno
S
S
Hattori
M
M
Wakiguchi
H
H
D000293:Adolescent; D000914:Antibodies, Viral / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D019562:Viral Load
D000914:Antibodies, Viral; D004279:DNA, Viral; D007166:Immunosuppressive Agents