Facoltà di scienze biomediche

Shp-2 is dispensable for establishing T cell exhaustion and for PD-1 signaling in vivo

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

In: Cell reports, 2018, vol. 23, no. 1, p. 39-49

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... Plus

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    Summary
    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.