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.
Miyazaki
A
A
Department of Pathology, Sapporo Medical University School of Medicine.
Sato
N
N
Takahashi
S
S
Sasaki
A
A
Kohama
G
G
Yamaguchi
A
A
Yagihashi
A
A
Kikuchi
K
K
D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D010641:Phenotype; D014062:Tongue Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006684:HLA-DR Antigens; D008024:Ligands