CD4 T-CELLS KILL MELANOMA-CELLS BY MECHANISMS THAT ARE INDEPENDENT OFFAS (CD95)

Previous studies have shown that CD4 T cells are associated with regre ssion in primary melanoma and rejection of tumors in adoptive transfer models. The mechanism by which they mediate their anti-tumor effects remains unclear, and some studies have suggested that Pas ligand (FasL )/Fas interactions were involved, In the present study, we have examin ed the cytotoxic mechanism involved in CD4 T-cell killing of melanoma cells and, in particular, the role of FasL/Fas interactions in this ki lling, We show that the CD4 T cells in 4 clones of T cells induced apo ptosis in autologous melanoma cells by MHC-restricted mechanisms but l ysed an allogeneic melanoma cell by a non-apoptotic mechanism. Melanom a cells expressed both Pas and FasL, but killing of melanoma cells did not involve Fas/FasL interactions, This was shown by a lack of correl ation between Fas expression and susceptibility to lysis and by failur e of a monoclonal antibody to Pas to block killing by the CD4 T cells, though the latter expressed Fast. Recombinant Fast did not induce kil ling of melanoma cells. (C) 1998 Wiley-Liss, Inc.