Poster Presentation 47th Lorne Genome Conference 2026

Comprehensive analysis of the epigenetic landscape in ageing CD8+ T cells (133058)

Minh Anh (Morgan) MB Bui 1 , Daniel DT Thiele 1 , David DC Chisanga 1 , Pushkar PD Dakle 1 , Adele AB Barugahare 1 , Gemma GS Schlegel 1 , Zhongming ZZ Zhang 1 , Stephen ST Turner 1 , Nicole NLG La Gruta 1
  1. Monash University, Clayton, VICTORIA, Australia

Ageing has a profound impact on the immune system. CD8+ T cells are an important component of the adaptive immune repertoire. Not only are CD8+ T cells severely affected by ageing, but some research suggests that they might be driving organismal ageing. At steady state, CD8+ T cells exist as either antigen-naive T (TN) cells, antigen-experienced memory T (TMEM) cells, or antigen-naive but differentiated virtual memory T (TVM) cells. Interestingly, distinct age-related T cell dysfunctions across these subsets are associated with heterogeneity in transcriptional and chromatin accessibility profiles. Since histone post-translational modifications (PTMs) can impact chromatin accessibility, thereby altering transcription, it is of great interest to investigate the epigenetic-associated molecular mechanisms behind age-related immune dysfunctions. To investigate steady-state T cell ageing, young (2 - 3 months old) and aged (18 - 24 months old) C57BL/6 mice were kept in a specific-pathogen-free facility. Cleavage Under Targets and Tagmentation (CUT&Tag) was utilised to map histone PTM (H3K9me3, H3K27me3, H3K4me1, H3K4me3, H2BK20ac, H3K27ac) deposition on a genome-wide scale before the generated DNA libraries were sequenced. Flow cytometric analysis showed the relative abundance of multiple histone PTMs across CD8+ T cell subsets remained similar with age. However, CUT&Tag revealed changes in the depositions of histone PTMs with age and across CD8+ T cell subsets. Differential analysis for all histone PTMs of interest identified the associated gene regions of differential depositions. Our results suggest that with age, CD8+ T cell dysfunction is associated with changes in a broad range of histone PTMs depositions. Therefore, the findings of this study will inform approaches to reverse age-related immune dysfunction.