Shp-2 is dispensable for establishing T cell exhaustion and for PD-1 signaling in vivo
Item Type: | Article |
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Title: | Shp-2 is dispensable for establishing T cell exhaustion and for PD-1 signaling in vivo |
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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. |
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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. |
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Keywords: | Shp-2, Ptpn11, T Cell Exhaustion, Inhibitory Receptors, PD-1, Checkpoint Therapy, Cancer, Chronic Infection, Animals, Mice |
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Source: | Cell Reports |
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ISSN: | 2211-1247 |
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Publisher: | Cell Press / Elsevier |
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Volume: | 23 |
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Number: | 1 |
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Page Range: | 39-49 |
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Date: | 3 April 2018 |
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Official Publication: | https://doi.org/10.1016/j.celrep.2018.03.026 |
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PubMed: | View item in PubMed |
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