Fig. 5: Neuron-reactive KIR⁺CD8⁺ T cells from cluster 1 in Ri-AIE patients are strongly activated and express high levels of pro-inflammatory cytokines.

a Volcano plot highlighting all significantly upregulated (orange) and downregulated genes (blue) between neuron-reactive KIR⁺CD8⁺ T cells from Ri-AIE vs AgD. Vertical ticked lines represent the fold-change threshold set at an average log₂FC(0.5) for upregulated or log₂FC(−0.5) for downregulated genes. Horizontal ticked line represents the adjusted p value threshold established at 0.05. All significantly differentially expressed genes from c–h are annotated on the plot. b Dot plot of KEGG pathway enrichment analysis highlighting the 5 most enriched pathways according to adjusted p value, in neuron-reactive KIR⁺CD8⁺ T cells from Ri AIE vs AgD. The enrichment score is scaled from blue to orange (strongest score), with each dot reflecting the percentage of gene overlap relative to each pathway. c–h Heatmaps displaying selected genes involved in key CD8⁺ T cell functions such as immune regulation (c), TCR activation (d) or inhibition (e), activation markers (f), pro-inflammatory signaling (g) or TOX-controlled genes (h). Highly expressed genes are represented in orange and low-expressed genes in blue. A star is displayed in the column for neuron-reactive KIR⁺CD8⁺ T cells from Ri-AIE when genes from this group were significantly differentially expressed as compared to neuron-reactive KIR⁺CD8⁺ T cells from AgDs.