ROLR OF OX40 IN IN VIVO CELL GROWTH AND ORGAN INFILTRATION OF ATL CELLS

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We have studied the role of OX40 in in vivo cell growth and organ infiltration of ATL cells and the results obtained aer as follows. 1. We have demonstrated that gp34, the ligand of OX40 is expressed on cultured vascular endothelial cells, and the OX40/gp34 system directly mediates cell adhesion between activated T cells or HTLV-I-infected cell line cells and HUVEC using stable transfectants of human OX40 and gp34, anti-OX40 antibodies and anti-gp34 antibodies. 2. The expression of c-jun and the activation of NF-kB are induced by gp34 binding to OX40. In addition, it has been demonstrated by experiments using various deletion mutants that the cytoplasmic protion of OX40 consisting of amino acid sequence 249-262 is required for NF-kB activation. 3. OX40 was expressed on fresh leukemic cells from 15 Of 17 ATL patients when examined by flowcytometric analysis and on leukemic cells infiltrating into skin in all the 4 patients examined. Furthermore, the cell adhesion between fresh leukemic cells and HUVEC was dtected in 3 of 4 ATL patients.These results clearly indicate the involvement of OX40/gp34 system in cell adhesion between ATL cells and vascular endothelial cells and strongly suggest its important role in the infiltration of ATL cells into various organs.