CYTOTOXICITY OF HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN-DR8-RESTRICTED CD4(-CELLS AGAINST HUMAN AUTOLOGOUS SQUAMOUS-CELL CARCINOMA() KILLER T)

Although CD8(+) killer T cells reacting against human autologous tumor cells have recently been studied in detail, little is known about the cytotoxic mechanism of CD4(+) T cells against such tumor cells. In or der to investigate this, we have established CD4(+) cytotoxic T lympho cyte TcOSC-20 lines. TcOSC-20 showed selective cytotoxic activity agai nst autologous OSC-20 cells, derived from a cancer of the tongue, in a n HLA-DR-restricted fashion. HLA-DR8 (DRB108032) is the only DR molec ule expressed on OSC-20 cells, and anti-DR8 monoclonal antibody could inhibit the cytotoxicity, suggesting that HLA-DRB108032 is the tumor rejection antigen-presenting molecule to TcOSC-20. The Fas ligand was expressed on TcOSC-20 lines, and its expression was induced upon mixed lymphocyte-tumor cell culture of autologous peripheral blood lymphocy tes. Furthermore, the cytotoxicity of TcOSC-20 was inhibited by anti-F as ligand antibody. These data imply that TcOSC-20 lines recognize the tumor antigenic peptide presented by HLA-DR8, and exert cytotoxicity against autologous tumor cells via a Fas-mediated cytotoxic pathway.