TY - JOUR
T1 - Glucocorticoid imprints a low glucose metabolism onto CD8 T cells and induces the persistent suppression of the immune response
AU - Konishi, Amane
AU - Suzuki, Junpei
AU - Kuwahara, Makoto
AU - Matsumoto, Akira
AU - Nomura, Shunsuke
AU - Soga, Tomoyoshi
AU - Yorozuya, Toshihiro
AU - Yamashita, Masakatsu
N1 - Funding Information:
We thank A. Tamai and K. Kameda (Advanced Research Center, Ehime University) for their excellent technical assistance. This work was supported by JSPS KAKENHI Grants ( 19K08909 , 20H035040 , 20H049480 , 20K092450 ), Japan and the Uehara Memorial Foundation, Japan .
Funding Information:
We thank A. Tamai and K. Kameda (Advanced Research Center, Ehime University) for their excellent technical assistance. This work was supported by JSPS KAKENHI Grants (19K08909, 20H035040, 20H049480, 20K092450), Japan and the Uehara Memorial Foundation, Japan.
Publisher Copyright:
© 2021 The Authors
PY - 2022/1/15
Y1 - 2022/1/15
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - Glucocorticoid
KW - Glycolysis
KW - Memory T cells
KW - Programed cell death 1
KW - Tumor immunity
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U2 - 10.1016/j.bbrc.2021.12.050
DO - 10.1016/j.bbrc.2021.12.050
M3 - Article
C2 - 34942532
AN - SCOPUS:85121822487
SN - 0006-291X
VL - 588
SP - 34
EP - 40
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -