Extended Data Fig. 6: Tissue-specific T cell metaclustering identifies a replicative senescent CD8⁺ T cell population.

(a) Heatmap of MetaCluster communities of CD3⁺ T cells from atherosclerotic plaque by surface marker expression tissue (n = 23). (b) Correlations between TCR clonality in plaque and the frequency of MetaCluster 25 in 8 patients by two-sided Pearson correlation test. (c) Representative viSNE plots of n = 10,000 cells showing the MC distribution and expression of selected markers. (d, e) Analysis of manually gated CD8⁺ T cells from cohorts 1 and 2 combined (n = 37 patients). (d) Representative viSNE plot overlaid by CD8⁺CD127⁺ and CD8⁺CD127^– populations. (e) Scatter bar plot of CD8⁺CD127^+/- frequencies from 37 patients, assessed by two-sided paired Student’s t test. Values are mean ± SD. (f) viSNE plots of n = 8,086 cells overlaid with expression of T cell functional markers. (g) Scatter bar plots of the median values of T cell functional markers available between cohorts 1 and 2. CCR7, CD26, CD38, PD1, CD69 were available from 24 patients; CD27 from 25 patients, CD25, HLADR from 37 patients. p values were determined using Wilcoxon test, and values are mean ± SD. (h) Correlations between TCR clonality and CD8⁺CD127^- cell frequency from 9 patients. Two-sided Spearman correlation test was used. (i) ViSNE plots of representative CD8⁺ T cell population in plaque of n = 9,025 cells overlaid with CD127 expression (top), or by subpopulation: CD127⁺ (blue), CD127^- (yellow), and Ki67⁺ (red) (bottom). (j) Percent of Ki67⁺ cells in CD127 subpopulations from 3 independent experiments (n = 3). Statistic determined using a two-sided paired Student’s t test. Values are mean ± SD. (k) Representative contour plots of CD8⁺CD127^- plaque T cells gated for CD57 expression, and the CD8⁺CD127^-CD57⁺ subpopulation gated for Ki67 expression.