Potential role of natural killer cells in controlling tumorigenesis by human T-cell leukemia viruses.
Human T-cell leukemia virus (HTLV) is the etiologic agent of adult T-cell leukemia (ATL), a malignancy of T lymphocytes that is characterized by a long latency period after virus exposure. Intraperitoneal inoculation of severe combined immunodeficient (SCID) mice with HTLV-transformed cell lines and ATL tumor cells was employed to investigate the tumorigenic potential of HTLV type I (HTLV-I)-infected cells. In contrast to inoculation of ATL (RV-ATL) cells into SCID mice, which resulted in the formation of lymphomas, inoculation of HTLV-I- and HTLV-II-transformed cell lines (SLB-I and JLB-II cells, respectively) did not result in tumor formation. Immunosuppression of SCID mice, either by whole-body irradiation or by treatment with an antiserum, anti-asialo GM1 (alpha-AGM1), which transiently abrogates natural killer cell activity in vivo, was necessary to establish the growth of tumors derived from HTLV-transformed cell lines. PCR and flow cytometric studies reveal that HTLV-I-transformed cells are eliminated from the peritoneal cavities of inoculated mice by 3 days postinoculation; in contrast, RV-ATL cells persist and are detected until the mice succumb to lymphoma development. The differing behaviors of HTLV-infected cell lines and ATL tumor cells in SCID mice suggest that ATL cells have a higher tumorigenic potential in vivo than do HTLV-infected cell lines because of their ability to evade natural killer cell-mediated cytolysis.
Feuer
G
G
Department of Medicine, UCLA School of Medicine.
Stewart
S A
SA
Baird
S M
SM
Lee
F
F
Feuer
R
R
Chen
I S
IS
D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D006800:Deltaretrovirus Infections / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D015458:Leukemia, T-Cell / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010529:Peritoneal Cavity / Q000166:cytology; D010641:Phenotype
D017493:Leukocyte Common Antigens