Studies on the mechanism of cell growth of ATL cells

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Summary of our studies on the mechanism of neoplastic cell growth in vivo of ATL cells are as follows. 1.We established a model of in vivo cell proliferation of ATL cells using SCID mice. 2.Fresh leukemic cells from ATL patients and HTLV-I-infected cell lines derived from leukemic cell clones showed tumorigenicity. HTLV-I-infected cell lines of nonleukemic cell origin and tax-transfected in vitro immortalized cells did not show tumorigenicity. 3.It appears that HTLV-I-expression is not needed for the cell growth of ATL cells in vivo and IL-2 autocrine mechanism in not involved in the cell growth in vivo. 4.We demonstrated the organ infiltration pattern of ATL cells in vivo using the radiolabeled anti-Tac antibody as a tracer. 5.We developed two monoclonal antibodies (MoAb) which block the unknown adhesion pathway between ATL cells and human umbilical vein endothelial cells (HUVEC). After characterizing the antigen, we succeeded in the cloning of its cDNA.The Agrecognized by the MoAb was found to be human OX40 homologue, a member of TNF receptor family. We then, for the first time, demonstrated that OX40 and its ligand (gp34) directly mediated the adhesion between ATL cells and HUVEC.Furthermore, we demonstrated the expression of gp34 on other vascular endothelial cells. OX40/gp34 may play a key role not only in the neoplastic cell growth and organ infiltration of ATL cells but also in the interaction between activated T cells and vascular endothelial cells which leads to infalmmatory lesions.