DNAX accessory molecule-1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vgamma9Vdelta2 T cells.
Eur J Immunol
; 39(5): 1361-8, 2009 May.
Article
en En
| MEDLINE
| ID: mdl-19404979
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T
/
Antígenos de Diferenciación de Linfocitos T
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Receptores de Antígenos de Linfocitos T gamma-delta
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Francia