Involvement of TNF-related apoptosis-inducing ligand in human CD4(+) T cell-mediated cytotoxicity

TNF-related apoptosis-inducing ligand (TRAIL) has been identified as a memb er of the TNF family that induces apoptosis in a variety of tumor cells, bu t its physiological functions are largely unknown. In the present study, we examined the expression and function of TRAIL in human CD4(+) T cell clone s by utilizing newly established anti-human TRAIL mAbs, Human CD4(+) T cell clones, HK12 and 4HM1, exhibited perforin-independent and Fas ligand (FasL )-independent cytotoxicity against certain target cells, including T lympho ma (Jurkat) and keratinocyte (HaCaT) cell lines, which are susceptible to T RAIL-mediated cytotoxicity, In contrast to FasL, the expression of which wa s inducible upon anti-CD3 stimulation, TRAIL was constitutively expressed o n HK12 and 4HM1 cells, and no further increase was observed after anti-CD3 stimulation, Spontaneous cytotoxic activities of resting HK12 and 4HM1 cell s against Jurkat and HaCaT cells were blocked by anti-TRAIL mAb but not by anti-FasL mAb, and bystander cytotoxic activities of anti-CD3-stimulated HK 12 and 4HM1 cells were abolished by the combination of anti-TRAIL and anti- FasL mAbs, These results indicate a differential regulation of TRAIL and Fa sL expression on human CD4+ T cell clones and that TRAIL constitutes an add itional pathway of T cell-mediated cytotoxicity.