Restricted diversification of T-cells in chronic active Epstein-Barr virus infection: Potential inclination to T-lymphoproliferative disease

Shouichi Ohga, Nobuhiro Kimura, Hidetoshi Takada, Mituyuki Nagano, Kohichi Ohshima, Akihiko Nomura, Kenji Muraoka, Hiromichi Take, Shunji Yamamori, Toshiro Hara

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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 Cβ 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 Vβ gene usages were preferential in all patients (Vβ7 and Vβ12: patient 1, Vβ4: patient 2, Vβ13: patients 3 and 4), compared with those in healthy controls. Vα18 gene expression was remarkably high in patients 1 and 2. Moreover, Jβ gene expression was skewing in the reigning Vβ clones in all patients. Vβ4- Jβ1.5 and Vβ13-Jβ1.5 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.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalAmerican Journal of Hematology
Volume61
Issue number1
DOIs
Publication statusPublished - Jan 1 1999

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this