Increased expression of a novel early activation surface membrane receptorin cutaneous T cell lymphoma cells

Using a newly generated monoclonal antibody we identified the 96 kDa transm embrane receptor SC5 expressed simultaneously on a human Sezary cell line a nd a minor T cell subset in normal individuals. SC5 antigen was detected mo stly on CD45RO+ lymphocytes from both CD4+ and CD8+ subsets as well as on n atural killer and B lineage cells. SC5 surface expression increased very ea rly after polyclonal stimulation of CD3+ cells due to the transfer of intra cellular SC5 molecules to the cell membrane. Engagement of SC5 receptor by its monoclonal antibody inhibited the anti-CD3-induced proliferation and cy tokine secretion of peripheral blood T cells and cell clones, whereas SC5 m onoclonal antibody did not affect the cytotoxic activity of CD8+ T cell clo nes. Extensive phenotypic analysis revealed that the percentage of SC5+ CD4 + circulating lymphocytes in Sezary syndrome patients was significantly inc reased in comparison with controls (p < 0.01) and correlated with the morph ologically detected percentage of Sezary syndrome cells in peripheral blood (p < 0.001). In one patient we clearly demonstrated that the circulating m alignant T cells coexpress SC5 molecules. Importantly, ligation of SC5 rece ptor in a cutaneous T cell lymphoma cell Line profoundly inhibited the anti -CD3-induced proliferation. Consequently, the expression of SC5 receptor in the peripheral blood of Sezary syndrome patients may serve not only to det ect the presence of circulating malignant CD4+ cells but also as a target f or immunotherapy.