Cutting Edge: Elevated Glycolytic Metabolism Limits the Formation of Memory CD8 + T Cells in Early Life

• Published in: The Journal of immunology (1950) Vol. 203; no. 10; pp. 2571 - 2576
• Main Authors: Tabilas, Cybelle, Wang, Jocelyn, Liu, Xiaojing, Locasale, Jason W, Smith, Norah L, Rudd, Brian D
• Format: Journal Article
• Language: English
• Published: United States 15.11.2019
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1900426

Neonates often develop poor immunity against intracellular pathogens. Because CD8 T cells are essential for eliminating infectious agents, it is crucial to understand why they behave differently in early life. Previous studies in mice have demonstrated that neonatal CD8 T cells fail to form memory because of an intrinsic propensity to differentiate into short-lived effectors. However, the underlying mechanisms remain undefined. We now show that neonatal CD8 T cells exhibit higher glycolytic activity than adult CD8 T cells postinfection, which may be due to age-related differences in Lin28b expression. Importantly, when glycolysis is pharmacologically inhibited, the impaired formation of neonatal memory CD8 T cells can be restored. Collectively, these data suggest that neonatal CD8 T cells are inherently biased toward undergoing glycolytic metabolism postinfection, which compromises their ability to develop into memory CD8 T cells in early life.