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- W4313385364 abstract "Abstract Upon activation, T cells enter a developmental program characterized by clonal expansion and effector cell differentiation followed by contraction and survival of long-lived memory T cells. This program is regulated by interplay of activation-induced signaling and metabolic changes. During the proliferative stage, naïve T cells undergo a metabolic switch to glycolysis which provides the molecular substrates to support T cell growth. The subsequent survival of memory T cells is supported by a switch from mTORC activity to AMPK activation and oxidative metabolism. Compared to naïve T cells, memory T cells have increased mitochondrial capacity; activation induced metabolic changes are less well characterized. Recall responses, such as CD4 T responses to influenza vaccination, are compromised in the elderly. Here, we examined whether the regulation of metabolic pathway contribute to this defect. Upon activation, CD4 memory T cells upregulate oxidative phosphorylation as well as glycolysis. Oxidative phosphorylation peaks 48 hours after activation in parallel to increases in mitochondrial mass. Subsequently, it is then sharply downregulated, while increased glycolysis is maintained. While CD4 memory T cell responses in older individuals (>65 years) display appropriate upregulation of glycolysis, they are associated with increased oxidative metabolic activity compared to younger individuals (< 30 years old). Mitochondrial function was superior as documented by increased spare respiratory capacity with normal mitochondrial mass as well as production of ATP and reactive oxygen species. We propose that the increased mitochondrial activity compromises memory T cell function in older individuals." @default.
- W4313385364 created "2023-01-06" @default.
- W4313385364 creator A5016250824 @default.
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- W4313385364 date "2016-05-01" @default.
- W4313385364 modified "2023-09-23" @default.
- W4313385364 title "Regulation of metabolic pathways in CD4 T memory cell responses of older individuals" @default.
- W4313385364 doi "https://doi.org/10.4049/jimmunol.196.supp.204.4" @default.
- W4313385364 hasPublicationYear "2016" @default.
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