PTPN2 regulates the generation of exhausted CD8⁺ T cell subpopulations and restrains tumor immunity.

ABSTRACT: CD8⁺ T cell exhaustion is a state of dysfunction acquired in chronic viral infection and cancer, characterized by the formation of Slamf6⁺ progenitor exhausted and Tim-3⁺ terminally exhausted subpopulations through unknown mechanisms. Here we establish the phosphatase PTPN2 as a new regulator of the differentiation of the terminally exhausted subpopulation that functions by attenuating type 1 interferon signaling. Deletion of Ptpn2 in CD8⁺ T cells increased the generation, proliferative capacity and cytotoxicity of Tim-3⁺ cells without altering Slamf6⁺ numbers during lymphocytic choriomeningitis virus clone 13 infection. Likewise, Ptpn2 deletion in CD8⁺ T cells enhanced Tim-3⁺ anti-tumor responses and i

SUBMITTER: LaFleur MW 

PROVIDER: S-EPMC6754306 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature