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...

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Bibliographic Details
Published in:Cancer science 1997-02, Vol.88 (2), p.191-197
Main Authors: Miyazaki, Akihiro, Sato, Noriyuki, Takahashi, Shuji, Sasaki, Aya, Kohama, Gen–iku, Yamaguchi, Akira, Yagihashi, Atsuhito, Kikuchi, Kokichi
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - immunology
Antigens
Antigens, Neoplasm - immunology
Biological and medical sciences
Carcinoma, Squamous Cell - immunology
CD4 antigen
CD4+ killer T cell
CD4-Positive T-Lymphocytes - immunology
CD8 antigen
Cell culture
Cell Line
Cytotoxicity
Dose-Response Relationship, Immunologic
DR8
Drb1 protein
FasL protein
Histocompatibility antigen HLA
HLA
HLA-DR Antigens - immunology
Host-tumor relations. Immunology. Biological markers
Humans
Killer Cells, Natural - immunology
Ligands
Lymphocytes
Lymphocytes T
Medical sciences
Monoclonal antibodies
Peripheral blood
Phenotype
Squamous cell carcinoma
Tongue Neoplasms - immunology
Tumor cells
Tumor Cells, Cultured
Tumors
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Summary: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.
ISSN:0910-5050
1347-9032
1349-7006
1876-4673
DOI:10.1111/j.1349-7006.1997.tb00365.x