DNAX accessory molecule-1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vgamma9Vdelta2 T cells.

Abstract

Human Vgamma9Vdelta2 T lymphocytes can be activated by nonpeptidic antigens such as the mevalonate pathway-derived isopentenyl pyrophosphate or synthetic phosphoantigen such as bromohydrin pyrophosphate. They display a strong cytotoxic activity against several tumor types, including hepatocellular carcinoma (HCC). Little is known about the mechanisms underlying Vgamma9Vdelta2 T-cell recognition of tumor cells, but there is strong evidence that activating NK receptors play a role in gammadelta T-cell cytotoxicity. In this study, we showed that the two NK receptors DNAX accessory molecule-1 (DNAM-1) and CD96 were expressed by Vgamma9Vdelta2 T cells. The ligands Nectin-like-5 specific of both DNAM-1 and CD96, and also Nectin-2, an additional ligand of DNAM-1, were present on all HCC cell lines analyzed. Furthermore, we demonstrated by mAb-mediated masking experiments that cytotoxicity against HCC cells as well as IFN-gamma production in gammadelta T cells were dependent on DNAM-1. Our experiments indicated that Nectin-like-5 but not Nectin-2 was involved in DNAM-1-dependent gammadelta T-cell functions. We did not reveal a role for CD96 in the killing of HCC cells. Finally, we showed by combined mAb-mediated blockade that DNAM-1 and NKG2D could cooperate in the cell lysis of HCC.

• Authors: Olivier Toutirais, Florian Cabillic, Gaëlle Le Friec, Samuel Salot, Pascal Loyer, Matthieu Le Gallo, Mireille Desille, Cécile Thomas de La Pintière, Pascale Daniel, Françoise Bouet, Véronique Catros
• Journal: European journal of immunology (Eur J Immunol) Vol. 39 Issue 5 Pg. 1361-8 (May 2009) ISSN: 1521-4141 [Electronic] Germany
• PMID: 19404979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• CD226 antigen
• CD96 antigen
• Cell Adhesion Molecules
• Nectins
• RNA, Small Interfering
• Receptors, Antigen, T-Cell, gamma-delta
• Receptors, Virus
• poliovirus receptor

Topics

• Antibodies, Monoclonal (pharmacology)
• Antigens, CD (biosynthesis, immunology)
• Antigens, Differentiation, T-Lymphocyte (biosynthesis, immunology)
• Carcinoma, Hepatocellular (immunology, therapy)
• Cell Adhesion Molecules (genetics, immunology)
• Cell Line, Tumor
• Cytotoxicity, Immunologic
• Flow Cytometry
• Humans
• Immunity, Innate (immunology)
• Immunotherapy (methods)
• Liver Neoplasms (immunology, therapy)
• Lymphocyte Activation
• Nectins
• RNA, Small Interfering (genetics)
• Receptors, Antigen, T-Cell, gamma-delta (immunology)
• Receptors, Virus (genetics, immunology)
• T-Lymphocytes (immunology)
• Transfection