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Autoreactive CD8+ T cells are restrained by an exhaustion-like program that is maintained by LAG3

ABSTRACT: CD8+ T cell exhaustion is a distinct differentation state resulting from chronic antigen exposure and leading to hierarchical loss of effector functions. Using a murine model of diabetes, we show that CD8+ T cells derived from the islets of diabetic mice have CD8+ T cells that are canonically exhausted and yet retain sufficient effector function to contribute to pathogenicity in autoimmune diabetes. Genetic deletion of the inhibitory receptor LAG3 restricted to only CD8+ T cells lead to accelerated disease, with LAG3 deficient CD8+ T cells having enhanced effector function and trafficking. These findings reveal a distinct role of LAG3 in restraining autoreactive CD8+ T cells and implicate LAG3 as a potential therapeutic target in autoimmunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE199357 | GEO | 2022/04/08

REPOSITORIES: GEO

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Autoreactive CD8+ T cells are restrained by an exhaustion-like program that is maintained by LAG3

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