NO. 75

CIMR Wednesday Lecture Series

Time:

Wednesday, Jun. 18 2025, 11:00 a.m.

Location:

Yifu Lecture Hall, North Basic Research Building 

Host：

Kaibin Shi (史凯斌)

Chinese Institutes for Medical Research, Beijing

Speaker：

Hongbo Hu (胡洪波)

Investigator

West China Hospital

Sichuan University

TITLE：

Human T cell development and aging

ABSTRACT:

Age-related thymic involution is a hallmark of T-cell aging, heightening vulnerability to cancers and emerging pathogens in the elderly. However, the precise mechanisms driving thymic involution and its impact on impaired peripheral T-cells remain unclear. By single cell RNA-sequencing (scRNA-seq) and T-cell receptor-sequencing (scTCR-seq), we captured and analyzed 283,331 cells from thymus and peripheral blood of young and elderly individuals. Our findings revealed an elevated proportion of early thymic progenitor (ETP) cells in the aged thymus, accompanied by reduced T-lineage potential. Meanwhile, inflammatory profiles of intrathymic CD4⁺ and CD8⁺ T-cells increased with age. Thymic microenvironment supporting T-cell development deteriorated with age, as evidenced by reduced thymic epithelial cells (TECs) and tissue restricted antigens (TRAs) expression. In the periphery, we identified transcriptional features of T-cell aging crossing T-cell populations. Furthermore, CD38 emerged as new marker for CD4⁺ and CD8⁺ recent thymic emigrants (RTEs). TCR-seq analysis indicated dramatic changes in TCR repertoire diversity within memory and effector T-cells and an expansion of virus specific T-cells in the elderly. Collectively, our data offer insights into human thymus involution and peripherical T-cell aging leading to potential strategies to restore compromised T-cell immunity.

SELECTED PAPERS