Details

Autor(en) / Beteiligte

• Rota, Giorgia
• Niogret, Charlène
• Dang, Anh Thu
• Barros, Cristina Ramon
• Fonta, Nicolas Pierre
• Alfei, Francesca
• Morgado, Leonor
• Zehn, Dietmar
• Birchmeier, Walter
• Vivier, Eric
• Guarda, Greta

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2018-04, Vol.23 (1), p.39-49

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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+ 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. [Display omitted] •Shp-2 modulates selected T cell exhaustion features•Shp-2 is not required for the global dysfunctional state of exhausted T cells•Anticancer α-PD-1 treatment is beneficial in mice with Shp-2-deficient T cells In vitro data indicate that Shp-2 is engaged by PD-1 and contributes to T cell exhaustion. Rota et al. show that Shp-2-deficient T cells acquire a dysfunctional state when exposed to chronic antigen in vivo and respond to PD-1 blockade, indicating the existence of additional signaling factors.