Cytokine expression and tumorigenicity of large granular lymphocytic leukemia cells from mice transgenic for the tax gene of human T-cell leukemia virus type I.
The human T-cell leukemia virus type I (HTLV-I) regulatory protein, Tax, has been speculated to play a major role in HTLV-I leukemogenesis. Indeed, several studies have suggested that upregulation of various cellular oncogenes and cytokines by Tax may explain the pathogenesis observed in HTLV-I-infected individuals, as well as several Tax-transgenic animal models. We report here the analysis of cytokine expression in a Tax-transgenic animal model with large granular lymphocytic (LGL) leukemia. Two different transgenic mice showed identical expression of interleukin-1alpha (IL-1alpha), IL-1beta, interferon gamma (IFNgamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in peripheral tail tumors. Interestingly, LGL cell lines derived from these same tumors expressed high levels of both IFNgamma and GM-CSF, which correlated with the level of Tax expression. These same LGL cell lines also expressed high levels of lymphocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1). Engraftment of these LGL cell lines into severe combined immunodeficient (SCID) mice led to the development of leukemia and lymphomas. Examination of these SCID mice showed that their pathology was nearly identical to that observed in the original Tax-transgenic mouse model. Both the Tax-transgenic and engrafted SCID mouse models allow for the analysis of cellular events that are required for tumor development associated with HTLV infection and suggest that Tax expression may be responsible for the upregulation of certain cytokines and adhesion molecules that affect the infiltrating capabilities of HTLV-I-infected cells.
Grossman
W J
WJ
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Ratner
L
L
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D016356:Gene Products, tax / Q000096:biosynthesis*; D016355:Genes, pX; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007945:Leukemia, Lymphoid / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D016207:Cytokines; D016356:Gene Products, tax; D007375:Interleukin-1; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor