CD70 contributes to age-associated T cell defects and overwhelming inflammatory responses

Di Wang, Juan Du, Yangzi Song, Beibei Wang, Rui Song, Yu Hao, Yongqin Zeng, Jiang Xiao, Hong Zheng, Hui Zeng, Hongxin Zhao, Yaxian Kong

Research output: Contribution to journalArticle

Abstract

Aging is associated with immune dysregulation, especially T cell disorders, which result in increased susceptibility to various diseases. Previous studies have shown that loss of co-stimulatory receptors or accumulation of co-inhibitory molecules play important roles in T cell aging. In the present study, CD70, which was generally regarded as a costimulatory molecule, was found to be upregulated on CD4+ and CD8+ T cells of elderly individuals. Aged CD70+ T cells displayed a phenotype of over-activation, and expressed enhanced levels of numerous inhibitory receptors including PD-1, 2B4 and LAG-3. CD70+ T cells from elderly individuals exhibited increased susceptibility to apoptosis and high levels of inflammatory cytokines. Importantly, the functional dysregulation of CD70+ T cells associated with aging was reversed by blocking CD70. Collectively, this study demonstrated CD70 as a prominent regulator involved in immunosenescence, which led to defects and overwhelming inflammatory responses of T cells during aging. These findings provide a strong rationale for targeting CD70 to prevent dysregulation related to immunosenescence.

Original languageEnglish (US)
Pages (from-to)12032-12050
Number of pages19
JournalAging
Volume12
Issue number12
DOIs
StatePublished - Jun 30 2020

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

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    Wang, D., Du, J., Song, Y., Wang, B., Song, R., Hao, Y., Zeng, Y., Xiao, J., Zheng, H., Zeng, H., Zhao, H., & Kong, Y. (2020). CD70 contributes to age-associated T cell defects and overwhelming inflammatory responses. Aging, 12(12), 12032-12050. https://doi.org/10.18632/aging.103368