Constitutive activation of Wnt signaling favors generation of memory CD8 T cells.

Détails

Ressource 1Télécharger: BIB_0080BC0E87C5.P001.pdf (1081.08 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_0080BC0E87C5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Constitutive activation of Wnt signaling favors generation of memory CD8 T cells.
Périodique
Journal of Immunology
Auteur(s)
Zhao D.M., Yu S., Zhou X., Haring J.S., Held W., Badovinac V.P., Harty J.T., Xue H.H.
ISSN
1550-6606[electronic], 0022-1767[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
184
Numéro
3
Pages
1191-1199
Langue
anglais
Résumé
T cell factor-1 (TCF-1) and lymphoid enhancer-binding factor 1, the effector transcription factors of the canonical Wnt pathway, are known to be critical for normal thymocyte development. However, it is largely unknown if it has a role in regulating mature T cell activation and T cell-mediated immune responses. In this study, we demonstrate that, like IL-7Ralpha and CD62L, TCF-1 and lymphoid enhancer-binding factor 1 exhibit dynamic expression changes during T cell responses, being highly expressed in naive T cells, downregulated in effector T cells, and upregulated again in memory T cells. Enforced expression of a p45 TCF-1 isoform limited the expansion of Ag-specific CD8 T cells in response to Listeria monocytogenes infection. However, when the p45 transgene was coupled with ectopic expression of stabilized beta-catenin, more Ag-specific memory CD8 T cells were generated, with enhanced ability to produce IL-2. Moreover, these memory CD8 T cells expanded to a larger number of secondary effectors and cleared bacteria faster when the immunized mice were rechallenged with virulent L. monocytogenes. Furthermore, in response to vaccinia virus or lymphocytic choriomeningitis virus infection, more Ag-specific memory CD8 T cells were generated in the presence of p45 and stabilized beta-catenin transgenes. Although activated Wnt signaling also resulted in larger numbers of Ag-specific memory CD4 T cells, their functional attributes and expansion after the secondary infection were not improved. Thus, constitutive activation of the canonical Wnt pathway favors memory CD8 T cell formation during initial immunization, resulting in enhanced immunity upon second encounter with the same pathogen.
Mots-clé
Animals, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/microbiology, Cell Differentiation/genetics, Cell Differentiation/immunology, Cell Survival/genetics, Cell Survival/immunology, Clonal Anergy/genetics, Clonal Anergy/immunology, Gene Expression Regulation/immunology, Immunologic Memory/genetics, Listeria monocytogenes/immunology, Lymphocyte Activation/genetics, Lymphocytic choriomeningitis virus/immunology, Lymphoid Enhancer-Binding Factor 1/biosynthesis, Lymphoid Enhancer-Binding Factor 1/genetics, Mice, Mice, Inbred C57BL, Mice, Transgenic, Signal Transduction/genetics, Signal Transduction/immunology, T Cell Transcription Factor 1/biosynthesis, T Cell Transcription Factor 1/genetics, T-Lymphocytes, Regulatory/immunology, T-Lymphocytes, Regulatory/microbiology, Wnt Proteins/genetics, Wnt Proteins/metabolism, beta Catenin/biosynthesis, beta Catenin/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/02/2010 10:12
Dernière modification de la notice
20/08/2019 12:22
Données d'usage