Restricted diversification of T-cells in chronic active Epstein-Barr virus infection: potential inclination to T-lymphoproliferative disease.
To assess the abnormal T-cell expansion in chronic active Epstein-Barr virus infection (CAEBV), T-cell antigen receptor (TCR) repertoire was analyzed in four patients with the disease. All fulfilled the diagnostic criteria of CAEBV, presenting with fever, hepatosplenomegaly, cytopenia, abnormal high titers of anti EBV-antibodies, and positive EBV genome of unknown cause. Southern blotting probed with EBV-terminal repeats and TCR Cbeta gene indicated clonal expansion of the infected cells in 3 and 2 patients, respectively. The number of CD4+ HLA-DR+ cells appreciably increased in patients 1 (59%) and 2 (24%), who had a coronary aneurysm and central nervous system involvement, respectively. TCR gene expression examined by the inverse polymerase chain reaction methods revealed that Vbeta gene usages were preferential in all patients (Vbeta7 and Vbeta12: patient 1, Vbeta4: patient 2, Vbeta13: patients 3 and 4), compared with those in healthy controls. Valpha18 gene expression was remarkably high in patients 1 and 2. Moreover, Jbeta gene expression was skewing in the reigning Vbeta clones in all patients. Vbeta4-Jbeta1.5 and Vbeta13-Jbeta1.5 genes were clonally expressed in patients 2 and 4, respectively. These results suggest that CAEBV is associated with the restricted diversity of T-cells, which may stem from the sustained expansion of oligoclonal T-cells possibly driven by conventional viral antigens, but not, superantigens. Although the study is limited by the small number of patients, the unbalanced T-cell repertoire might contribute to the evolution of T-lymphoproliferative disease, otherwise, imply the innate defective immunity to EBV in CAEBV patients.
Ohga
S
S
Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka, Japan. ohgas@mailserver.med.kyushu-u.ac.jp
Kimura
N
N
Takada
H
H
Nagano
M
M
Ohshima
K
K
Nomura
A
A
Muraoka
K
K
Take
H
H
Yamamori
S
S
Hara
T
T
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D015139:Blotting, Southern; D002648:Child; D002908:Chronic Disease; D004247:DNA / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000276:immunology / Q000473:pathology*; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006529:Hepatomegaly; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013163:Splenomegaly; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
D000914:Antibodies, Viral; D004279:DNA, Viral; D011948:Receptors, Antigen, T-Cell; D004247:DNA