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

Human T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiolo gic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by whic h the virus causes the malignant transformation is largely unknown. In orde r to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a ra t model system in which ATL-like disease was reproducibly observed, followi ng inoculation of various rat HTLV-1-immortalized cell lines. When previous ly established cell lines, F344-S1 and TARS-1, but not TART-1 or W7TM-1, we re inoculated, systemic multiple tumor development was observed in adult nu de (nu/nu) rats. FPM1 cells, newly established from a heterozygous (nu/+) r at syngeneic to nu/nu rats, caused transient tumors only at the injection s ite 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) seria lly 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 vi vo tumorigenicity. Using the syngeneic system, we further showed the inhibi tion of tumor development by transferring splenic T cells from immunized ra ts, 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 inv estigation of leukemogenesis and antitumor immune responses in HTLV-1 infec tion.