Age-Related Gene Alteration in Naïve and Memory T cells Using Precise Age-Tracking Model

Xiaofeng Yang; Xin Wang; Lei Lei; Lina Sun; Anjun Jiao; Kun Zhu; Tao Xie; Haiyan Liu; Xingzhe Zhang; Yanhong Su; Cangang Zhang; Lin Shi; Dan Zhang; Huiqiang Zheng; Jiahui Zhang; Xiaobin Liu; Xin Wang; Xiaobo Zhou; Chenming Sun; Baojun Zhang

doi:10.3389/fcell.2020.624380

Age-Related Gene Alteration in Naïve and Memory T cells Using Precise Age-Tracking Model

Front Cell Dev Biol. 2021 Feb 11:8:624380. doi: 10.3389/fcell.2020.624380. eCollection 2020.

Authors

Xiaofeng Yang^{1

2

3}, Xin Wang^{1

2

3}, Lei Lei^{1

2

3}, Lina Sun^{4

5}, Anjun Jiao^{1

2

3}, Kun Zhu^{1

2}, Tao Xie^{1

2}, Haiyan Liu^{1

2}, Xingzhe Zhang^{1

2}, Yanhong Su^{1

2}, Cangang Zhang^{1

2}, Lin Shi^{1

2}, Dan Zhang^{1

2}, Huiqiang Zheng^{1

2}, Jiahui Zhang^{1

2}, Xiaobin Liu^{1

2}, Xin Wang^{1

2}, Xiaobo Zhou^{1

2}, Chenming Sun^{1

2}, Baojun Zhang^{1

2

3}

Affiliations

¹ Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.
² Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, China.
³ Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, China.
⁴ Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, United States.
⁵ Center for Molecular Medicine, University of Georgia, Athens, GA, United States.

Abstract

In aged individuals, age-related changes in immune cells, especially T cell deficiency, are associated with an increased incidence of infection, tumor, and autoimmune disease, as well as an impaired response to vaccination. However, the features of gene expression levels in aged T cells are still unknown. Our previous study successfully tracked aged T cells generated from one wave of developing thymocytes of young age by a lineage-specific and inducible Cre-controlled reporter (TCRδ ^CreER R26 ^ZsGreen mouse strain). In this study, we utilized this model and genome-wide transcriptomic analysis to examine changes in gene expression in aged naïve and memory T cell populations during the aging process. We identified profound gene alterations in aged CD4 and CD8 T cells. Both aged CD4⁺ and CD8⁺ naïve T cells showed significantly decreased organelle function. Importantly, genes associated with lymphocyte activation and function demonstrated a significant increase in aged memory T cells, accompanied by upregulation of immunosuppressive markers and immune checkpoints, revealing an abnormal T cell function in aged cells. Furthermore, aging significantly affects T cell survival and death signaling. While aged CD4 memory T cells exhibited pro-apoptotic gene signatures, aged CD8 memory T cells expressed anti-apoptotic genes. Thus, the transcriptional analysis of gene expression and signaling pathways in aged T cell subsets shed light on our understanding of altered immune function with aging, which will have great potential for clinical interventions for older adults.

Keywords: CD4 T cells; CD8 T cells; TCRδCreERR26ZsGreen mice; aged T cells; naïve T cells.