Fig. 5: Lower T cell reactivity in patients with SLE receiving SARS-CoV-2 mRNA vaccines.

a, Schematic showing the 24-h AIM assay-based detection of antigen-reactive T cells upon incubation of PBMCs with a megapool of spike-derived peptides and the flow cytometric analysis of surface-expressed markers of activation and immune profiling. b, Representative FACS plots showing the gating strategy applied to characterize the AIM⁺ spike-reactive CD8⁺ (41BB⁺CD69⁺) T cells or AIM⁺ spike-reactive CD4⁺ (OX40⁺CD40L⁺) T cells and AIM⁺ spike-reactive cT_FH (CXCR5⁺ of AIM⁺CD4⁺) cells among the CD3⁺ T cells. c–e, Scatter plots showing the frequency of spike-specific AIM⁺ T cells quantified at each indicated time point in the HD and SLE cohorts for AIM⁺CD8⁺ T cells (c), AIM⁺CD4⁺ T cells (d) and AIM⁺CD4⁺ cT_FH (e) cells. The vaccination time points in c–e indicate the following binned time points (T), as indicated in Extended Data Fig. 1a: 0 (T0, baseline), 1 (T1–T3), 2 (T4–T5), 3 (T6–T7), 4 (T8–T9), 5 (B1–B5) and 6 (B6–B9). The number of samples is indicated as ‘Total (n)’. f, PaCMAP and FlowSOM representations of AIM⁺CD8⁺ T cells (HD, n = 137; SLE, n = 163) and AIM⁺CD4⁺ T cells (HD, n = 136; SLE, n = 169) from the HD (n = 126) and SLE (n = 161) cohorts from combined Vax1 + Vax2 + Vax3. A total of 15 clusters are indicated in the plots, and the relative marker expression and classification of the clusters are shown in Extended Data Fig. 7f,g. g, Representative dot plots showing the differentiation of AIM⁺ T cells using CD45RA and CCR7 expression. h, Bar plots showing the distribution of the four subsets (T_N/T_SCM, T_CM, T_EM and T_EMRA) of AIM⁺CD8⁺ T cells. Individual samples from the HD (Vax1, n = 17; Vax2, n = 47; Vax3, n = 43) and SLE (Vax1, n = 12; Vax2, n = 65, Vax3, n = 38) cohorts. i, Bar plots showing the distribution of the four subsets (T_N/T_SCM, T_CM, T_EM and T_EMRA) of AIM⁺CD4⁺ T cells. Individual samples from the HD (Vax1, n = 19; Vax2, n = 54; Vax3, n = 48) and SLE (Vax1, n = 20; Vax2, n = 81, Vax3, n = 45) cohorts. A two-sided Mann–Whitney U test was applied to compare each subset of T cells between the SLE and HD groups, and significance is shown in the SLE bars. When indicated, the LOD was set to logarithmic 0.001 for B cells and 0.003 for T cells. The LOS was based on median values of baseline + 2 × s.d. Vertical lines indicate the s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. MP, megapool; T_N, naive T cells; T_SCM, stem cell-like memory T cells; T_CM, central memory T cells; T_EMRA, T_EM cells reexpressing CD45RA.