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健康儿童TCRβ库的年龄相关动态变化及光谱特征:对免疫衰老的启示

Age-Related Dynamics and Spectral Characteristics of the TCRβ Repertoire in Healthy Children: Implications for Immune Aging.

作者信息

Fang Mingyan, Miao Yu, Zhu Lin, Mei Yunpeng, Zeng Hui, Luo Lihua, Ding Yuan, Zhou Lina, Quan Xueping, Zhao Qin, Zhao Xiaodong, An Yunfei

机构信息

BGI Research, Shenzhen, China.

School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China.

出版信息

Aging Cell. 2025 Apr;24(4):e14460. doi: 10.1111/acel.14460. Epub 2025 Jan 2.

Abstract

T-cell receptor (TCR) diversity is crucial for adaptive immunity, yet baseline characterizations in pediatric populations remain sparse. We sequenced the TCRβ chain of 325 healthy Chinese children aged 0-18, categorized into six age groups. We also analyzed cellular composition and TCRβ associations using flow cytometry in 81 of these samples. Our results indicate a decrease in TCRβ diversity with age, characterized by an increase in high-frequency clonotypes and notable changes in CDR3 length and V(D)J gene usage. These changes are influenced by early life vaccinations and antigen exposures. Additionally, we found a significant association between reduced TCRβ diversity and a decrease in CD4 T naïve cells. We also developed a predictive model that identifies specific TCRβ features as potential biomarkers for biological age, validated by their significant correlation with changes in the immune repertoire. These findings enhance our understanding of age-related variations in the TCRβ repertoire among children, providing resourceful information for research on pediatric TCR in health and disease.

摘要

T细胞受体(TCR)多样性对于适应性免疫至关重要,但儿科人群的基线特征描述仍然很少。我们对325名年龄在0至18岁的健康中国儿童的TCRβ链进行了测序,这些儿童被分为六个年龄组。我们还使用流式细胞术分析了其中81个样本的细胞组成和TCRβ关联。我们的结果表明,TCRβ多样性随年龄增长而降低,其特征是高频克隆型增加以及CDR3长度和V(D)J基因使用情况发生显著变化。这些变化受早期疫苗接种和抗原暴露的影响。此外,我们发现TCRβ多样性降低与CD4初始T细胞减少之间存在显著关联。我们还开发了一种预测模型,该模型将特定的TCRβ特征识别为生物年龄的潜在生物标志物,并通过它们与免疫库变化的显著相关性进行了验证。这些发现加深了我们对儿童TCRβ库中与年龄相关变化的理解,为健康和疾病状态下儿科TCR的研究提供了丰富的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1073/11984678/da999563e405/ACEL-24-e14460-g003.jpg

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