Glucocorticoid imprints a low glucose metabolism onto CD8 T cells and induces the persistent suppression of the immune response

Biochem Biophys Res Commun. 2022 Jan 15:588:34-40. doi: 10.1016/j.bbrc.2021.12.050. Epub 2021 Dec 17.

Abstract

Glucocorticoids (GCs), immunosuppressive, and anti-inflammatory agents have various effects on T cells. However, the long-term influence of GCs on the T cell-mediated immune response remain to be elucidated. We demonstrated that the administration of GC during the TCR-mediated activation phase induced long-lasting suppression of glycolysis, even after the withdrawal of GC. The acquisition of the effector functions was inhibited, while the expression of PD-1 was increased in CD8 T cells activated in the presence of GC. Furthermore, adoptive transfer experiments revealed that GC-treated CD8 T cells reduced memory T cell formation and anti-tumor activity. These findings reveal that GCs have long-lasting influence on the T cell-mediated immune response via modulation of T cell metabolism.

Keywords: CD8 T cells; Glucocorticoid; Glycolysis; Memory T cells; Programed cell death 1; Tumor immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism*
  • Female
  • Glucocorticoids / pharmacology*
  • Glucose / metabolism*
  • Glycolysis / drug effects
  • Immunity* / drug effects
  • Immunologic Memory / drug effects
  • Immunosuppression Therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Prednisolone / pharmacology

Substances

  • Antigens
  • Glucocorticoids
  • Prednisolone
  • Glucose