新生儿 CD8 T 细胞谱系与成人不同,并且受呼吸道合胞病毒感染小鼠固有 T 细胞特性的影响。

Neonatal CD8 T-cell hierarchy is distinct from adults and is influenced by intrinsic T cell properties in respiratory syncytial virus infected mice.

机构信息

Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States of America.

出版信息

PLoS Pathog. 2011 Dec;7(12):e1002377. doi: 10.1371/journal.ppat.1002377. Epub 2011 Dec 1.

Abstract

Following respiratory syncytial virus infection of adult CB6F1 hybrid mice, a predictable CD8+ T cell epitope hierarchy is established with a strongly dominant response to a K(d)-restricted peptide (SYIGSINNI) from the M2 protein. The response to K(d)M2(82-90) is ∼5-fold higher than the response to a subdominant epitope from the M protein (NAITNAKII, D(b)M(187-195)). After infection of neonatal mice, a distinctly different epitope hierarchy emerges with codominant responses to K(d)M2(82-90) and D(b)M(187-195). Adoptive transfer of naïve CD8+ T cells from adults into congenic neonates prior to infection indicates that intrinsic CD8+ T cell factors contribute to age-related differences in hierarchy. Epitope-specific precursor frequency differs between adults and neonates and influences, but does not predict the hierarchy following infection. Additionally, dominance of K(d)M2(82-90)-specific cells does not correlate with TdT activity. Epitope-specific Vβ repertoire usage is more restricted and functional avidity is lower in neonatal mice. The neonatal pattern of codominance changes after infection at 10 days of age, and rapidly shifts to the adult pattern of extreme K(d)M2(82-90)-dominance. Thus, the functional properties of T cells are selectively modified by developmental factors in an epitope-specific and age-dependent manner.

摘要

在成年 CB6F1 杂交小鼠感染呼吸道合胞病毒后,建立了一个可预测的 CD8+T 细胞表位层次结构,对 M2 蛋白中 K(d)限制的肽(SYIGSINNI)产生强烈的优势反应。对 K(d)M2(82-90)的反应比 M 蛋白(NAITNAKII,D(b)M(187-195))的次要表位高约 5 倍。在感染新生小鼠后,出现了明显不同的表位层次结构,对 K(d)M2(82-90)和 D(b)M(187-195)产生共显性反应。在感染前将来自成年小鼠的幼稚 CD8+T 细胞过继转移到同基因的新生小鼠中,表明内在的 CD8+T 细胞因子有助于年龄相关的层次结构差异。表位特异性前体频率在成年和新生小鼠之间不同,并影响但不能预测感染后的层次结构。此外,K(d)M2(82-90)-特异性细胞的优势与 TdT 活性无关。与成年小鼠相比,新生小鼠的表位特异性 Vβ repertoire 使用更受限,功能亲和力更低。在 10 天大的感染后,新生小鼠的共显性模式发生变化,并迅速转变为成年小鼠的极端 K(d)M2(82-90)优势模式。因此,T 细胞的功能特性以表位特异性和年龄依赖性的方式被发育因素选择性修饰。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a7b/3228797/bef4e81b3746/ppat.1002377.g001.jpg

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