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, Ta x, has been speculated to play a major role in HTLV-I leukemogenesis. Indeed, several studies have suggested that upregulation of various ce llular oncogenes and cytokines by Tax may explain the pathogenesis obs erved in HTLV-l-infected individuals, as well as several Tax-transgeni c animal models. We report here the analysis of cytokine expression in a Tax-transgenic animal model with large granular lymphocytic (LGL) l eukemia. Two different transgenic mice showed identical expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, interferon gamma (IFN gam ma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in peripheral tail tumors. Interestingly, LGL cell lines derived from the se same tumors expressed high levels of both IFN gamma and GM-CSF, whi ch correlated with the level of Tax expression. These same LGL cell li nes also expressed high levels of lymphocyte function-associated antig en-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1). Engraftme nt 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 t hat observed in the original Tax-transgenic mouse model. Both the Tax- transgenic and engrafted SCID mouse models allow for the analysis of c ellular 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 aff ect the infiltrating capabilities of HTLV-I-infected cells. (C) 1997 b y The American Society of Hematology.