Cytotoxicity of histocompatibility leukocyte Antigen-DR8-restricted CD4⁺ killer T cells against human autologous squamous cell carcinoma

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 order to investigate this, we have established CD4⁺ cytotoxic T lymphocyte TcOSC-20 lines. TcOSC-20 showed selective cytotoxic activity against autologous OSC-20 cells, derived from a cancer of the tongue, in an HLA-DR-restricted fashion. HLA-DR8 (DRB1(*)08032) is the only DR molecule expressed on OSC-20 cells, and anti-DR8 monoclonal antibody could inhibit the cytotoxicity, suggesting that HLA-DRB1(*)08032 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 lymphocytes. Furthermore, the cytotoxicity of TcOSC-20 was inhibited by anti-Fas 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.