Ly49D engagement on T lymphocytes induces TCR-independent activation and CD8 effector functions that control tumor growth.

Détails

ID Serval
serval:BIB_9105060A85B6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Ly49D engagement on T lymphocytes induces TCR-independent activation and CD8 effector functions that control tumor growth.
Périodique
Journal of immunology
Auteur(s)
Merck E., Voyle R.B., MacDonald H.R.
ISSN
1550-6606[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
182
Numéro
1
Pages
183-192
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Recent data showing expression of activating NK receptors (NKR) by conventional T lymphocytes raise the question of their role in the triggering of TCR-independent responses that could be damaging for the host. Transgenic mice expressing the activating receptor Ly49D/DAP12 offer the opportunity to better understand the relevance of ITAM signaling in the biology of T cells. In vitro experiments showed that Ly49D engagement on T lymphocytes by a cognate MHC class I ligand expressed by Chinese hamster ovary (CHO) cells or by specific Ab triggered cellular activation of both CD4 and CD8 populations with modulation of activation markers and cytokine production. The forced expression of the ITAM signaling chain DAP12 is mandatory for Ly49D-transgenic T cell activation. In addition, Ly49D stimulation induced T lymphocyte proliferation, which was much stronger for CD8 T cells. Phenotypic analysis of anti-Ly49D-stimulated CD8 T cells and their ability to produce high levels of IFN-gamma and to kill target cells indicate that Ly49D ligation generates effector cytotoxic CD8 T cells. Ly49D engagement by itself also triggered cytotoxic activity of activated CD8 T cells. Adoptive transfer experiments confirmed that Ly49D-transgenic CD8 T cells are able to control growth of CHO tumor cells or RMA cells transfected with Hm1-C4, the Ly49D ligand normally expressed by CHO. In conclusion, Ly49D engagement on T cells leads to T cell activation and to a full range of TCR-independent effector functions of CD8 T cells.
Mots-clé
Animals, CHO Cells, Cell Differentiation/genetics, Cell Differentiation/immunology, Cell Line, Tumor, Cricetinae, Cricetulus, Cytotoxicity Tests, Immunologic, Ligands, Lymphocyte Activation/genetics, Lymphocyte Activation/immunology, Mastocytoma/immunology, Mastocytoma/pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, NK Cell Lectin-Like Receptor Subfamily A/genetics, NK Cell Lectin-Like Receptor Subfamily A/metabolism, Receptors, Antigen, T-Cell/physiology, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, T-Lymphocytes, Cytotoxic/cytology, T-Lymphocytes, Cytotoxic/immunology, Thymoma/immunology, Thymoma/pathology
Pubmed
Web of science
Création de la notice
15/01/2010 16:16
Dernière modification de la notice
20/08/2019 15:54
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