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

Authors

  • G. Rota
  • C. Niogret
  • A.T. Dang
  • C.R. Barros
  • N.P. Fonta
  • F. Alfei
  • L. Morgado
  • D. Zehn
  • W. Birchmeier
  • E. Vivier
  • G. Guarda

Journal

  • Cell Reports

Citation

  • Cell Rep 23 (1): 39-49

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.


DOI

doi:10.1016/j.celrep.2018.03.026