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Journal of Virology, October 2000, p. 9610-9616, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Prevention of Adult T-Cell Leukemia-Like Lymphoproliferative Disease in Rats by Adoptively Transferred T Cells from a Donor Immunized with Human T-Cell Leukemia Virus Type 1 Tax-Coding DNA Vaccine

Takashi Ohashi,1 Shino Hanabuchi,1 Hirotomo Kato,1 Hiromi Tateno,1 Fumiyo Takemura,1,2 Tomonori Tsukahara,1 Yoshihiro Koya,1 Atsuhiko Hasegawa,1 Takao Masuda,1 and Mari Kannagi1,2,*

Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, Tokyo 113,1 and CREST, Japan Science and Technology Corporation, Saitama 332,2 Japan

Received 7 March 2000/Accepted 17 July 2000

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) in infected individuals after a long incubation period. To dissect the mechanisms of the development of the disease, we have previously established a rat model of ATL-like disease which allows examination of the growth and spread of HTLV-1 infected tumor cells, as well assessment of the effects of immune T cells on the development of the disease. In the present study, we induced HTLV-1 Tax-specific cytotoxic T lymphocyte (CTL) immunity by vaccination with Tax-coding DNA and examined the effects of the DNA vaccine in our rat ATL-like disease model. Our results demonstrated that DNA vaccine with Tax effectively induced Tax-specific CTL activity in F344/N Jcl-rnu/+ (nu/+) rats and that these CTLs were able to lyse HTLV-1 infected syngeneic T cells in vitro. Adoptive transfer of these immune T cells effectively inhibited the in vivo growth of HTLV-1-transformed tumor in F344/N Jcl-rnu/rnu (nu/nu) rats inoculated with a rat HTLV-1 infected T cell line. Vaccination with mutant Tax DNA lacking transforming ability also induced efficient anti-tumor immunity in this model. Our results indicated a promising effect for DNA vaccine with HTLV-1 Tax against HTLV-1 tumor development in vivo.

* 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, October 2000, p. 9610-9616, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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