Neonatal naive CD8+ T cells have effector-like gene expression that prevents memory cell formation [RNA-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. Total 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（memory CD8+ T cells）的缺陷。本研究探究了感染前及感染过程中，新生儿与成人之间小RNA、转录因子及趋化因子受体的调控差异。研究发现，感染前的初始CD8+ T细胞（naive CD8+ T cells），其多种微小RNA（microRNAs）的表达谱存在显著差异，且这些微小RNA的靶基因也呈现广泛的表达差异。初始CD8+ T细胞的此类靶基因及其他基因表达改变，使得新生儿CD8+ 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，且在细胞收缩阶段对凋亡的保护作用减弱。最终，新生儿初始CD8+ T细胞的这些改变会驱使效应CD8+ T细胞发生终末分化，却以无法生成长效记忆细胞为代价。本研究对感染前及感染过程中的成人与新生儿CD8+ T细胞进行了总RNA测序。