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An altered metabolism could contribute to the low activation of neonatal CD8+T cells

Sanchez-Villanueva, J. A.; Rodriguez-Jorge, O.; Ramirez-Pliego, O.; Rosas-Salgado, G.; Abou-Jaoude, W.; Hernandez, C.; Naldi, A.; Thieffry, D.; Santana, M. A.

2019-08-08 immunology
10.1101/726885 bioRxiv
Show abstract

A low response of neonatal T cells to infections contributes to a high incidence of morbidity and mortality of neonates. Here we evaluated the impact of the cytoplasmic and mitochondrial levels of Reactive Oxygen Species (ROS) of adult and neonatal CD8+T cells on their activation potential. We further constructed a logical model to decipher the interplay of metabolism and ROS on T cell signaling. Our model captures the interplay between antigen recognition, ROS and metabolic status in T cell responses. This model displays alternative stable states corresponding to different cell fates, i.e. quiescent, activated and anergic states, depending on ROS status. Stochastic simulations with this model further indicate that differences in ROS status at the cell population level tentatively explain the lower activation rate of neonatal compared to adult CD8+T cells upon TCR engagement.

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