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(American Journal of Pathology. 2003;162:1629-1638.)
© 2003 American Society for Investigative Pathology

Preferential Expansion of V9-JP/V2-J3 T Cells in Nasal T-Cell Lymphoma and Chronic Active Epstein-Barr Virus Infection

Michiko K. Oyoshi^*, Hiroshi Nagata^*, Nobuhiro Kimura, Yu Zhang^*, Ayako Demachi^*, Toshiro Hara, Hirokazu Kanegane^¶, Yoshinobu Matsuo^||, Tomohiro Yamaguchi^*, Tomohiro Morio^**, Atsuyoshi Hirano, Norio Shimizu^* and Kohtaro Yamamoto^*

From the Department of Virology,^* Division of Medical Science, Medical Research Institute, and the Department of General Medicine,^** School of Medicine, Tokyo Medical and Dental University, Tokyo; the Department of Otorhinolaryngology, Sannoh Hospital, Chiba; the First Department of Internal Medicine, School of Medicine, Fukuoka University, Fukuoka; the Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Pediatrics,^¶ Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama; the Fujisaki Cell Center,|| Hayashibara Biochemical Laboratories, Okayama; and the Department of Gastroenterology and Hepatology, School of Medicine, Yamaguchi University, Yamaguchi, Japan

We recently established an Epstein-Barr virus (EBV)-positive T-cell line from a nasal T/natural killer (NK)-cell lymphoma (Nagata H, Konno A, Kimura N, Zhang Y, Kimura M, Demachi A, Sekine T, Yamamoto K, Shimizu N: Characterization of novel natural killer (NK)-cell and T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus. Blood 2001, 97:708–713). Subsequently, we established two novel EBV-positive T-cell lines from the peripheral blood of patients with chronic active EBV infection. Analysis of the terminal repeat of EBV showed that the three cell lines consisted of monoclonal populations, and flow cytometry showed that they had a common phenotype of T cells: CD3⁺ CD4^- CD8^- CD16^- CD19^- CD56⁺ CD57^- HLA-DR⁺ T-cell receptor (TCR) ß^- TCR ⁺. Analysis for the expression of TCR by flow cytometry showed that all three cell lines were V9⁺/V2⁺, but negative for VI, V1, or V3 TCR. Southern blot analysis for TCR genes showed that the three cell lines had a common rearrangement of V9-JP and J3 genes. Polymerase chain reaction and sequence analysis of the junction between V and J genes revealed that the J3 genes were rearranged with the V2 genes. In contrast, none of the EBV-negative T-cell lines, Molt-14, Peer, or Loucy, which were analyzed for controls, had V9 or V2 TCR, or a rearrangement of J3 genes. These results indicated that V9-JP/V2-J3⁺ T cells were preferentially affected by EBV and expanded in patients with nasal T-cell lymphoma and chronic active EBV infection. J3⁺ T cells are known to be a very minor population in T cells of peripheral blood, whereas V9-JP/V2-J1⁺ cells are the major population. The close association of EBV with this particular T-cell population may provide a key to the etiology of EBV-positive lymphoproliferative diseases.

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