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<p>Age-related thymic involution increases vulnerability to cancers and infection in older adults, yet the driving mechanisms and its impact on peripheral T cells remain unclear. Using single-cell sequencing, we here analyzed 387,762 cells from human thymus and peripheral blood of young and aged individuals. Within thymus, we found aging reduced T-lineage potential in early thymic progenitors but increased innate lymphocyte lineage potential. Aged thymus were enriched in mature T cells with low <i>SOX4</i> expression and inflammatory profiles but depleted of thymic epithelial cells and expression of tissue-restricted antigens. In the periphery, we identified transcriptional features of T cell aging and established a naive T cell-based model for immune age prediction. Furthermore, we identified CD38 as a marker of recent thymic emigrants. Finally, single-cell T cell receptor (TCR) repertoire sequencing identified shifts in TCR repertoire diversity within memory/effector T cells and expanded virus-specific T cells during aging. Collectively, our data offer insights into human thymic involution and peripheral T cell aging and could inform strategies to restore compromised T cell immunity.</p>

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Single-cell analysis of human thymus and peripheral blood unveils the dynamics of T cell development and aging

  • 期刊论文

  • 发表日期：

    2025年10月24日

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  • Yujun Deng,
  • Zhengcan Peng,
  • Kang Ming,
  • Xiaona Qiao,
  • Bin Ye,
  • Yan Liu,
  • Haiyue Wang,
  • Peng Yang,
  • Yu Zhang,
  • Kun Zhou,
  • Quanwei Huang,
  • Wei Guo,
  • Yi Xie,
  • Hong Chen,
  • Hui Yu,
  • Liangbin Lin,
  • Xinkai Zou,
  • Keyue Wang,
  • Pengbo Guan,
  • Birong Dong,
  • Xiaolong Chen,
  • Xiaowen Wang,
  • Jia Hu,
  • Yuzhang Wu,
  • Huiyuan Zhang,
  • Hongbo Hu

摘要

Age-related thymic involution increases vulnerability to cancers and infection in older adults, yet the driving mechanisms and its impact on peripheral T cells remain unclear. Using single-cell sequencing, we here analyzed 387,762 cells from human thymus and peripheral blood of young and aged individuals. Within thymus, we found aging reduced T-lineage potential in early thymic progenitors but increased innate lymphocyte lineage potential. Aged thymus were enriched in mature T cells with low SOX4 expression and inflammatory profiles but depleted of thymic epithelial cells and expression of tissue-restricted antigens. In the periphery, we identified transcriptional features of T cell aging and established a naive T cell-based model for immune age prediction. Furthermore, we identified CD38 as a marker of recent thymic emigrants. Finally, single-cell T cell receptor (TCR) repertoire sequencing identified shifts in TCR repertoire diversity within memory/effector T cells and expanded virus-specific T cells during aging. Collectively, our data offer insights into human thymic involution and peripheral T cell aging and could inform strategies to restore compromised T cell immunity.