title: 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.
abstract: 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.
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohashi
authors.forename: S
authors.initials: S
authors.lastname: Hanabuchi
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Koya
authors.forename: F
authors.initials: F
authors.lastname: Takemura
authors.forename: K
authors.initials: K
authors.lastname: Hirokawa
authors.forename: T
authors.initials: T
authors.lastname: Yoshiki
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Kannagi
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D015490:HTLV-I Infections / Q000473:pathology / Q000628:therapy* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007114:Immunization; D016219:Immunotherapy, Adoptive; D015458:Leukemia, T-Cell / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000473:pathology / Q000628:therapy* / Q000821:virology; D009362:Neoplasm Metastasis; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D013154:Spleen