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 2018-04-03 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. application/pdf https://localhost:5000/ark:/12658/srd1318946 https://susi.usi.ch/global/documents/318946 https://susi.usi.ch/documents/318946/files/Rota_CR_2018.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2018.03.026 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318946 info:eu-repo/semantics/openAccess CC BY-NC-ND Cell reports. - 2018, vol. 23, no. 1, p. 39-49 Shp-2 Ptpn11 T cell exhaustion Inhibitory receptors PD-1 : Checkpoint therapy Cancer Chronic infection info:eu-repo/classification/udc/57 Shp-2 is dispensable for establishing T cell exhaustion and for PD-1 signaling in vivo http://purl.org/coar/resource_type/c_6501