Cytotoxicity of Histocompatibility Leukocyte Antigen–DR8–restricted CD4+ Killer T Cells against Human Autologous Squamous Cell Carcinoma

Abstract

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–DRS monoclonal antibody could inhibit the Cytotoxicity, suggesting that HLA–DRB1★ 08032 is the tumor rejection antigen–presenting moleculeto 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.