Glucocorticoid imprints a low glucose metabolism onto CD8 T cells and induces the persistent suppression of the immune response
Amane Konishi, Junpei Suzuki, Makoto Kuwahara, Akira Matsumoto, Shunsuke Nomura, Tomoyoshi Soga, Toshihiro Yorozuya, Masakatsu Yamashita
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.