The study used eQTLs from single-cell transcriptomes of CD4+ T cells across five activation time points in 119 European individuals to select instruments for MR analysis. 482,971 eQTLs were identified, and after filtering, 11,021 eQTLs mapping to 1,817 genes were selected for dynamic eQTL MR analysis. The study also re-selected instruments with a more relaxed P-value cut-off and LD correlation threshold, identifying 45,913 instruments for T2D and 46,766 for CAD. The study aimed to validate main MR findings using eight sensitivity MR methods, revealing 150 unique genes altering T2D risk and 62 unique genes altering CAD risk. Differential gene expression analysis showed 49% of T2D genes exhibited evidence of differential expression between T2D and non-T2D individuals. The study further validated MR findings using non-dynamic eQTL datasets, identifying 158 gene–T2D pairs and 77 gene–CAD pairs with MR evidence. The study highlighted the importance of CD4+ T cell activation status in identifying causal genes for cardiometabolic diseases and identified immune-related drug targets for T2D and CAD.