INDUCTION OF ATL-LIKE LYMPHOPROLIFERATIVE DISEASE AND ITS PREVENTION BY ADOPTIVE IMMUNOTHERAPY IN T-CELL DEFICIENT NUDE RATS INOCULATED WITH SYNGENIC HTLV-I-IMMORTALIZED CELLS

Abstract

SP-09 Human T-cell leukemia virus type I (HTLV-I) has been shown to be the oncogenic agent of adult T cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In this study, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-I immortalized cell lines. When we inoculated previously established cell lines, some of them developed systemic multiple tumors in adult nude (nu/nu) rats. FPM1 cells, newly established from a hetero (nu/+) rat syngenic to nude rats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in new born 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 the in vitro HTLV-I immortalized cell lines possessed in vivo tumorigenicity. Using the syngenic 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 tumor. This nude rat model of human ATL will be useful for further investigation of both leukemogenesis and anti-tumor immune responses in HTLV-I infection.