Fig 2: TCF1 and LEF1 promote IL-10 production by B-1a cells and their control of CNS inflammation.a, UMAP showing clonal BCR usage in clusters of peritoneal B cells and expression of Tcf7, Cd5 and Ctla4. b, Gene module scores associated with gene signatures. c, PDL1 histograms and gMFI in the indicated cell subsets (n = 8). d,e, Flow cytometry plots and quantification of IL-10+ cells in TCF1high or TCF1low PC B1 cells (n = 6; d) and IL-10+ cells within PC B1 cells from TCF1WTLEF1WT (n = 11) and TCF1ΔLEF1Δ mice (n = 5; e). f, Expression of CD5, CD21, CD1d and B220 by CD19lowIL-10+ (blue), CD19highIL-10+ (red) and IL-10− (grey) cells with or without stimulation. g, TCF1 and LEF1 histograms (left) and quantification (right) in the cell subset shown in panel f (n = 3). h, Pseudocolour plots and quantification of IL-10+ splenic B cells from TCF1WTLEF1WT (n = 6) and TCF1ΔLEF1Δ (n = 4) mice. i,j, Correlation analysis between TCF1 or LEF1 expression and the percentage of IL-10+ cells (n = 6; i) or expression of CD5 and the percentage of IL-10+ in peritoneal B-1a cells from TCF1WTLEF1WT (n = 5) and TCF1ΔLEF1Δ (n = 5; j). k, Mean clinical scores of mice treated with either PBS (n = 5) or adoptively transferred with peritoneal B-1 cells from TCF1WTLEF1WT (n = 5) or TCF1ΔLEF1Δ (n = 5). l–n, Contour plots of GRM2A-positive cells within the indicated cell populations from the peritoneal cavity (l,m) and the spleen (n). o, Identification of GRM2A-positive B-1 cells in the EAE mouse brain; representative cells are from the area labelled ‘i’. Representative cells from the areas labelled ‘ii–iv’ are shown in Extended Data Fig. 7h. Each symbol represents an individual mouse, and the bars represent the median values (c–e,g,h). Data are presented as mean ± s.e.m. (k). Data are representative of n = 2 experiments (c–e,g–k) and n = 3 mice (l). Statistical analysis was performed using two-tailed Pearson correlation analysis (i,j), two-tailed Mann–Whitney t-test (h), one-way ANOVA with Tukey multiple-comparison test (c–e,g) and two-way ANOVA (k). The exact P values are shown.Source data

Fig 3: Expression of PD-1/PD-L1 and T-cell proliferative capacity according to physical activity levels in COPD patients. Patients were stratified by physical activity level (PAL) into three groups: moderate activity (MA; PAL > 1.65, yellow), moderate sedentary (MS; PAL 1.35–1.65, orange), and severe sedentary (SS; PAL < 1.35, red). (A) Frequency of PD-1–expressing CD4⁺ T cells (left) and CD8⁺ T cells (right) in MA (n = 20), MS (n = 40), and SS (n = 25) groups. (B) Frequency of PD-L1–expressing CD14⁺ monocytes in the same patient groups. (C) Proliferation of CD4⁺ (left) and CD8⁺ (right) T cells from peripheral blood mononuclear cells (PBMCs) after 96 h stimulation with 2 µg/mL pokeweed mitogen in MA (n = 19), MS (n = 36), and SS (n = 20) patients. (D) Correlation matrix between CD4⁺ and CD8⁺ T-cell proliferation and clinical, physical activity, and immune parameters (n = 75). Only significant Spearman’s correlations (P < 0.05) are shown. (E) T-cell proliferation (CD4⁺, left; CD8⁺, right) following 96 h culture under basal conditions or with PD-1 blockade (Nivolumab) in MA (n = 9), MS (n = 12), and SS (n = 10) groups. Paired data are shown. Data are presented as medians with 95% confidence intervals. Differences are analyzed using Kruskal–Wallis tests with Dunn’s post hoc correction or Wilcoxon matched-pairs signed-rank test, as appropriate. Adjusted P values are shown; n.s., not significant.

Fig 4: T-cell proliferative responses before and after a physical activity intervention in COPD patients. T-lymphocyte proliferation was assessed in peripheral blood mononuclear cells (PBMCs) collected pre- (orange) and post-intervention (green). (A–B) Proliferative CD4⁺ (A) and CD8⁺ (B) T-cell responses after 96 h stimulation with 2 µg/mL pokeweed mitogen in patients who decreased (ΔPAL ≤ 0, n = 17) or increased (ΔPAL > 0, n = 19) their physical activity level. (C–D) CD4⁺ (C) and CD8⁺ (D) T-cell proliferation pre- and post-intervention, cultured for 96 h under basal conditions or in the presence of a PD-1 blocking antibody (Nivolumab) (n = 21). Data are presented as medians with 95% confidence intervals. Statistical analysis was performed using two-way ANOVA with Sidak’s multiple comparisons test. Adjusted and interaction P values are shown; n.s., not significant.

Fig 5: Modulation of PD-1/PD-L1 axis expression following a physical activity intervention in COPD patients. Patients were categorized based on the change in physical activity level (PAL) after intervention: decreased activity (ΔPAL ≤ 0, n = 23) and increased activity (ΔPAL > 0, n = 36). (A) Plasma concentrations of soluble PD-1 and (B) PD-L1 before and after the intervention. (C–E) Frequency of PD-1⁺ CD4⁺ T cells (C), PD-1⁺ CD8⁺ T cells (D), and PD-L1⁺ CD14⁺ monocytes (E) pre- and post-intervention in patients who decreased (n = 23) or increased (n = 32) their PAL. Data are presented as medians with 95% confidence intervals. Comparisons were performed using two-way ANOVA with Sidak’s multiple comparisons test. Adjusted and interaction P values are reported; n.s., not significant.