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

被引：34

作者：

Ohashi, T

Hanabuchi, S

Kato, H

Koya, Y

Takemura, F

Hirokawa, K

Yoshiki, T

Tanaka, Y

Fujii, M

Kannagi, M

机构：

[1] Tokyo Med & Dent Univ, Dept Immunotherapeut, Div Med Res, Bunkyo Ku, Tokyo 113, Japan

[2] Univ Tokyo, Fac Agr, Dept Vet Internal Med, Tokyo 113, Japan

[3] Japan Sci & Technol Corp, CREST, Saitama 332, Japan

[4] Hokkaido Univ, Sch Med, Dept Pathol, Sapporo, Hokkaido 060, Japan

[5] Kitasato Univ, Sch Med, Dept Biosci, Sagamihara, Kanagawa 228, Japan

[6] Niigata Univ, Sch Med, Dept Virol, Niigata 951, Japan

来源：

JOURNAL OF VIROLOGY | 1999年 / 73卷 / 07期

关键词：

D O I：

10.1128/JVI.73.7.6031-6040.1999

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：6031 / 6040

页数：10

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