Single cell transcriptomic changes of CD8T cells in male and female patients with coronary artery disease and diabetes

Abstract Objective: The objective of this study was to determine the role of CD8+ T cells in subjects with coronary artery disease (CAD) with and without diabetes (DM). Methods: PBMCs of 60 men and women who underwent cardiac catheterization were interrogated by single cell RNA sequencing combined with 49 protein markers (CITE-Seq). Four pairs of groups were matched for all clinical and demographic parameters. Results: 140,610 single cell transcriptomes were successfully analyzed. Among them, 17,349 CD8+ T cells were identified as CD19− CD3+ CD4− CD8+, yielding 17 clusters. The proportion of cells in the CD137+ effector memory (EM) cluster were significantly decreased in CAD+ subjects when compared to matched CAD− subjects. This same cluster was significantly decreased in DM+ CVD− groups when compared to the matched DM− CVD− group. The NK-like Emra1 group was significantly more abundant in CVD+ subjects and in females compared to males. One of the regulatory CD8 T cell clusters was significantly reduced in diabetics. 30 genes were significantly upregulated in both CAD and DM. The DM gene signature was partially additive to the CAD gene signature. IFTM3 and RUNX3 showed more importance in females, TCF7 and LTB in males. Conclusions: We conclude that CAD is clearly reflected in PBMC transcriptomes and that significant differences exist in immune cell transcriptomes between women and men and between diabetic and non-diabetic subjects. Support by the NIH P01 HL 136275