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Journal of Virology, July 1999, p. 6031-6040, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Induction of Adult T-Cell Leukemia-Like Lymphoproliferative Disease and Its Inhibition by Adoptive Immunotherapy in T-Cell-Deficient Nude Rats Inoculated with Syngeneic Human T-Cell Leukemia Virus Type 1-Immortalized Cells

Takashi Ohashi,1 Shino Hanabuchi,1 Hirotomo Kato,1,2 Yoshihiro Koya,1 Fumiyo Takemura,1,3 Katsuiku Hirokawa,4 Takashi Yoshiki,5 Yuetsu Tanaka,6 Masahiro Fujii,1,7 and Mari Kannagi1,3,*

Department of Immunotherapeutics1 and Pathology and Immunology,4 Tokyo Medical and Dental University, Medical Research Division, and Department of Veterinary Internal Medicine, Faculty of Agriculture, University of Tokyo, Tokyo 113,2 CREST, Japan Science and Technology Corporation, Saitama 332,3 Department of Pathology, Hokkaido University School of Medicine, Sapporo 060,5 Department of Biosciences, School of Science, Kitasato University, Kanagawa 228,6 and Department of Virology, Niigata University School of Medicine, Niigata 951,7 Japan

Received 1 December 1998/Accepted 26 March 1999

Human T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiologic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-1-immortalized cell lines. When previously established cell lines, F344-S1 and TARS-1, but not TART-1 or W7TM-1, were inoculated, systemic multiple tumor development was observed in adult nude (nu/nu) rats. FPM1 cells, newly established from a heterozygous (nu/+) rat syngeneic to nu/nu rats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in newborn nu/nu rats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newborn nu/nu rats acquired the potency to grow in adult nu/nu rats. These results indicated that only some with additional changes but not all of the in vitro HTLV-1-immortalized cell lines possessed in vivo tumorigenicity. Using the syngeneic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumors. This novel and reproducible nude rat model of human ATL would be useful for investigation of leukemogenesis and antitumor immune responses in HTLV-1 infection.

* Corresponding author. Mailing address: Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113, Japan. Phone: 81 (3) 5803-5798. Fax: 81 (3) 5803-0235. E-mail: kann.impt{at}med.tmd.ac.jp.

Journal of Virology, July 1999, p. 6031-6040, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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