Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853.
Department of Pediatrics, Indiana University, Indianapolis, IN 46202.
J Immunol. 2019 Nov 15;203(10):2571-2576. doi: 10.4049/jimmunol.1900426. Epub 2019 Oct 9.
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.
新生儿通常对细胞内病原体产生较差的免疫力。由于 CD8 T 细胞对于消除感染因子至关重要,因此了解它们在生命早期为何表现不同非常重要。先前在小鼠中的研究表明,由于内在倾向于分化为短命效应物,新生儿 CD8 T 细胞无法形成记忆。然而,潜在的机制仍未确定。我们现在表明,感染后新生儿 CD8 T 细胞表现出比成人 CD8 T 细胞更高的糖酵解活性,这可能是由于 Lin28b 表达的年龄相关差异所致。重要的是,当糖酵解被药理学抑制时,受损的新生儿记忆 CD8 T 细胞的形成可以得到恢复。总的来说,这些数据表明,新生儿 CD8 T 细胞在感染后天生偏向于进行糖酵解代谢,这损害了它们在生命早期发展为记忆 CD8 T 细胞的能力。