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.
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.
Imada
K
K
First Department of Internal Medicine, Kyoto University, Japan.
Takaori-Kondo
A
A
Akagi
T
T
Shimotohno
K
K
Sugamura
K
K
Hattori
T
T
Yamabe
H
H
Okuma
M
M
Uchiyama
T
T
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line / Q000637:transplantation; D015973:Gene Expression Regulation, Leukemic; D015967:Gene Expression Regulation, Viral; D016355:Genes, pX; D006085:Graft Survival; D016867:Immunocompromised Host; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology*; D008221:Lymphoid Tissue / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology* / Q000473:pathology / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000502:physiology*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000637:transplantation; D011994:Recombinant Proteins / Q000494:pharmacology; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000637:transplantation* / Q000821:virology; D014407:Tumor Cells, Cultured / Q000637:transplantation
D007376:Interleukin-2; D009363:Neoplasm Proteins; D011994:Recombinant Proteins