ATL AND HTLV-I - IN-VIVO CELL-GROWTH OF ATL CELLS

The mechanism of leukemogenesis or neoplastic cell growth in adult T c ell leukemia (ATL) still remains unclear, although Tax of human T cell leukemia/lymphoma virus type I (HTLV-I), the etiologic virus, has bee n reported to affect the expression of various cellular genes which en code molecules involved in cell growth or cell death. We have studied the cell growth of HTLV-I-infected human T cells in severe combined im muno-deficiency (SCID) mice and found that fresh leukemic cells or cel l lines derived from leukemic cell clones bur not HTLV-I-infected cell lines of nonleukemic cell origin showed tumorigenicity, and neither H TLV-I nor IL-2 expression was needed for cell growth in vivo, indicati ng that accumulating changes in addition to the initial events induced by HTLV-I infection were required for the development of ATL. The int eraction between ATL cells and vascular endothelial cells appears to b e one of the important factors which determine the pattern of organ in filtration by leukemic cells. E-selectin and its ligand are one of the major cell adhesion pathways between ATL cells and human umbilical ve in endothelial cells (HUVEC). Another pathway that had not been identi fied was studied using newly developed monoclonal antibodies capable o f blocking cell adhesion. The molecules which directly mediate adhesio n between ATL cells and HUVEC were determined to be OX40 and gp34, a m ember of the tumor necrosis factor receptor (TNF-R) family and TNF fam ily, respectively. The OX40/gp34 system may play a key role in the tra fficking and homing of not only ATL cells but also activated normal T cells.