Altered NKG2D function in NK cells induced by chronic exposure to NKG2D ligand-expressing tumor cells.

Détails

ID Serval
serval:BIB_025488CD9396
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Altered NKG2D function in NK cells induced by chronic exposure to NKG2D ligand-expressing tumor cells.
Périodique
Blood
Auteur(s)
Coudert J.D., Zimmer J., Tomasello E., Cebecauer M., Colonna M., Vivier E., Held W.
ISSN
0006-4971
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
106
Numéro
5
Pages
1711-1717
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
NKG2D is an activation receptor that allows natural killer (NK) cells to detect diseased host cells. The engagement of NKG2D with corresponding ligand results in surface modulation of the receptor and reduced function upon subsequent receptor engagement. However, it is not clear whether in addition to modulation the NKG2D receptor complex and/or its signaling capacity is preserved. We show here that the prolonged encounter with tumor cell-bound, but not soluble, ligand can completely uncouple the NKG2D receptor from the intracellular mobilization of calcium and the exertion of cell-mediated cytolysis. However, cytolytic effector function is intact since NKG2D ligand-exposed NK cells can be activated via the Ly49D receptor. While NKG2D-dependent cytotoxicity is impaired, prolonged ligand exposure results in constitutive interferon gamma (IFNgamma) production, suggesting sustained signaling. The functional changes are associated with a reduced presence of the relevant signal transducing adaptors DNAX-activating protein of 10 kDa (DAP-10) and killer cell activating receptor-associated protein/DNAX-activating protein of 12 kDa (KARAP/DAP-12). That is likely the consequence of constitutive NKG2D engagement and signaling, since NKG2D function and adaptor expression is restored to normal when the stimulating tumor cells are removed. Thus, the chronic exposure to tumor cells expressing NKG2D ligand alters NKG2D signaling and may facilitate the evasion of tumor cells from NK cell reactions.
Mots-clé
Animals, CHO Cells, Cell Adhesion Molecules/immunology, Cell Adhesion Molecules/pharmacology, Cell Line, Tumor, Coculture Techniques, Cricetinae, Cytotoxicity, Immunologic/drug effects, Interferon-gamma/biosynthesis, Killer Cells, Natural/drug effects, Killer Cells, Natural/immunology, Ligands, Mice, Mice, Inbred C57BL, NK Cell Lectin-Like Receptor Subfamily K, Neoplasms/genetics, Neoplasms/metabolism, Receptors, Immunologic/drug effects, Receptors, Immunologic/immunology, Receptors, Natural Killer Cell, Signal Transduction/drug effects, Signal Transduction/physiology, Structure-Activity Relationship, Time Factors, Transfection, Tumor Escape/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/01/2008 16:24
Dernière modification de la notice
20/08/2019 13:24
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