Neonatal naive CD8+ T cells have effector-like gene expression that prevents memory cell formation [miRNA-Seq]

Neonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, naive cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in naive cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal naive cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. Small RNAs were sequenced from adult and neonatal CD8+ T cells before and during infection新生儿在应对胞内病原体感染时，天生存在生成记忆性CD8+ T细胞的缺陷。本研究针对感染前后新生儿与成人的小RNA、转录因子及趋化因子受体的调控差异展开探究。研究发现，感染前初始T细胞 (naive cells) 的多种微小RNA (microRNA) 表达谱存在显著差异，且这些微小RNA的靶基因亦呈现广泛的表达差异。上述靶基因及初始T细胞中其他基因的表达变化，使得新生儿T细胞更易被激活，表达可趋化至感染部位的趋化因子受体，且在免疫应答收缩阶段对凋亡的保护作用更弱。最终，新生儿初始T细胞的表达改变会驱动效应细胞发生终末分化，却以无法生成长效记忆性细胞为代价。本研究在感染前后，分别对成人与新生儿的CD8+ T细胞中的小RNA进行了测序。