Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_695980B27F50
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo.
Périodique
Cell Reports
Auteur(s)
Rota G., Niogret C., Dang A.T., Barros C.R., Fonta N.P., Alfei F., Morgado L., Zehn D., Birchmeier W., Vivier E., Guarda G.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
23
Numéro
1
Pages
39-49
Langue
anglais
Résumé
In chronic infection and cancer, T cells acquire a dysfunctional state characterized by the expression of inhibitory receptors. In vitro studies implicated the phosphatase Shp-2 downstream of these receptors, including PD-1. However, whether Shp-2 is responsible in vivo for such dysfunctional responses remains elusive. To address this, we generated T cell-specific Shp-2-deficient mice. These mice did not show differences in controlling chronic viral infections. In this context, Shp-2-deleted CD8 <sup>+</sup> T lymphocytes expanded moderately better but were less polyfunctional than control cells. Mice with Shp-2-deficient T cells also showed no significant improvement in controlling immunogenic tumors and responded similarly to controls to α-PD-1 treatment. We therefore showed that Shp-2 is dispensable in T cells for globally establishing exhaustion and for PD-1 signaling in vivo. These results reveal the existence of redundant mechanisms downstream of inhibitory receptors and represent the foundation for defining these relevant molecular events.

Mots-clé
PD-1, Ptpn11, Shp-2, T cell exhaustion, cancer, checkpoint therapy, chronic infection, inhibitory receptors
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/04/2018 17:28
Dernière modification de la notice
20/08/2019 15:24
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