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.
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.
Ohashi
T
T
Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, Tokyo 113, Japan.
Hanabuchi
S
S
Kato
H
H
Tateno
H
H
Takemura
F
F
Tsukahara
T
T
Koya
Y
Y
Hasegawa
A
A
Masuda
T
T
Kannagi
M
M
D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D005260:Female; D016356:Gene Products, tax / Q000235:genetics / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D007114:Immunization; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000517:prevention & control*; D008232:Lymphoproliferative Disorders / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D016356:Gene Products, tax; D019444:Vaccines, DNA; D014765:Viral Vaccines