Article Dans Une Revue Cell Reports Année : 2018

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

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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 alpha-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.

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hal-02118004 , version 1 (11-12-2024)

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Giorgia Rota, Charlene Niogret, Anh Thu Dang, Cristina Ramon Barros, Nicolas Pierre Fonta, et al.. Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo. Cell Reports, 2018, 23 (1), pp.39-49. ⟨10.1016/j.celrep.2018.03.026⟩. ⟨hal-02118004⟩
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