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

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Item Type:Article
Title:Shp-2 is dispensable for establishing T cell exhaustion and for PD-1 signaling in vivo
Creators Name:Rota, G. and Niogret, C. and Dang, A.T. and Barros, C.R. and Fonta, N.P. and Alfei, F. and Morgado, L. and Zehn, D. and Birchmeier, W. and Vivier, E. and Guarda, G.
Abstract: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.
Keywords:Shp-2, Ptpn11, T Cell Exhaustion, Inhibitory Receptors, PD-1, Checkpoint Therapy, Cancer, Chronic Infection, Animals, Mice
Source:Cell Reports
ISSN:2211-1247
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:23
Number:1
Page Range:39-49
Date:3 April 2018
Official Publication:https://doi.org/10.1016/j.celrep.2018.03.026
PubMed:View item in PubMed

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