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

doi:10.1016/j.celrep.2018.03.026

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Journal article

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

Rota, Giorgia Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
Niogret, Charlène Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
Dang, Anh Thu Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
Ramon Barros, Cristina Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
Fonta, Nicolas Pierre Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland - Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Alfei, Francesca Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany
Morgado, Leonor Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
Zehn, Dietmar Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany
Birchmeier, Walter Cancer Research Program, Max Delbrueck Center for Molecular Medicine (MDC) in the Helmholtz Society, 13125 Berlin, Germany
Vivier, Eric Centre d’Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, 13288 Marseille, France - Service d’Immunologie, Hôpital de la Timone, Assistance Publique-H^opitaux de Marseille, 13005 Marseille, France - Innate Pharma Research Labs, Innate Pharma, Marseille, France
Guarda, Greta Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland - Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland

03.04.2018

Published in:

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

English 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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