Contribution of ROS and metabolic status to neonatal and adult CD8+ T cell activation

PLoS One. 2019 Dec 16;14(12):e0226388. doi: 10.1371/journal.pone.0226388. eCollection 2019.

Abstract

In neonatal T cells, a low response to infection contributes to a high incidence of morbidity and mortality of neonates. Here we have evaluated the impact of the cytoplasmic and mitochondrial levels of Reactive Oxygen Species of adult and neonatal CD8+ T cells on their activation potential. We have also constructed a logical model connecting metabolism and ROS with T cell signaling. Our model indicates 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 levels. Stochastic simulations with this model further indicate that differences in ROS status at the cell population level contribute to the lower activation rate of neonatal, compared to adult, CD8+ T cells upon TCR engagement. These results are relevant for neonatal health care. Our model can serve to analyze the impact of metabolic shift during cancer in which, similar to neonatal cells, a high glycolytic rate and low concentrations of glutamine and arginine promote tumor tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging* / immunology
  • Aging* / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Female
  • Humans
  • Immune Tolerance / drug effects
  • Infant, Newborn* / immunology
  • Infant, Newborn* / metabolism
  • Lymphocyte Activation / drug effects*
  • Male
  • Oxidation-Reduction / drug effects
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology*

Substances

  • Reactive Oxygen Species

Grants and funding

CONACYT Grants 168182 and 257188 and the ECOS/ANUIES/SEP/CONACYT grants M11S01 and M17S02. The D.T. laboratory was supported by grants from the French Plan Cancer, in the context of the projects CoMET (2014–2017) and SYSTAIM (2015–2019), as well as by a grant from the French Agence Nationale pour la Recherche, in the context of the project TMod (2016–2020).