Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in severe combined immunodeficient mice and characterization of the cells proliferating in vivo

Abstract

The mechanism involved in leukemogenesis and neoplastic cell growth of adult T-cell leukemia (ATL) still remains unclear. We examined the tumorigenicity of human T-cell leukemia virus type I (HTLV-I)-infected cell lines in an in vivo cell proliferation model using severe combined immunodeficient (SCID) mice. Eleven HTLV-I-infected cell lines were injected into SCID mice and we found that 4 of them were capable of proliferating in SCID mice. Three of four transplantable cell lines are derived from the leukemic cell clone and 6 of 6 HTLV-I-infected cell lines of nonleukemic cell origin could not engraft in SCID mice. Interestingly, it was shown that some HTLV-I-infected and interleukin-2 (IL-2)-dependent cell lines could successfully engraft in SCID mice. The expression of IL-2 mRNA was not detected in these cell lines growing either in vivo or in vitro. HTLV-I viral products were not detected in 3 of 4 transplantable cell lines proliferating in vivo. Peripheral blood T cells immortalized by introduction of tax gene of HTLV-I were found to have no tumorigenic potential in SCID mice. These data suggest that (1) HTLV-I-infected cell lines of nonleukemic cell origin do not have enough leukemogenic changes to acquire the tumorigenic potential in SCID mice; (2) the IL-2 autocrine mechanism is not directly involved in the tumor cell growth; (3) viral gene expression is not needed for the maintenance of neoplastic cell growth; and (4) the expression of tax gene is not sufficient for the neoplastic cell growth in vivo.