Fig. 2: CD8⁺ T_SCM cells increased host stress susceptibility.

A Schematic of the scRNA-seq workflow. Components of this figure were created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com. B Nine transcriptionally distinct T cell clusters were overlaid on the t-SNE representation. C Hierarchical clustering of the log-fold change in DEGs ([log₂(fold change)] ≥ 1 and FDR < 0.05) in MDD patients and psychiatrically healthy controls for each cell type. D Proportions of CD8⁺ T_SCM cells in pHCs and MDD patients in the scRNA-seq analysis. *P = 0.0312 versus the pHCs group, n = 3/group. E Proportions of CD8⁺ T_SCM cells in pHCs and MDD patients. ***P < 0.0001 versus the pHCs group, n = 39/group. The proportion of CD8⁺ T_SCM cells correlated with HAMD-24 total scores (F), and the factor scores of feelings of despair (G) and sleep disturbance (H) in MDD patients. n = 39. Correlations between CD8⁺ T_SCM cell proportions and the scores of MADRS (I) and PHQ-9 (J) in MDD patients. n = 39. The proportion of CD8⁺ T_SCM cells correlated with HAMA total scores (K), and the factor scores of physical anxiety (L) and psychological anxiety (M) in MDD patients. n = 39. N Proportions of CD8⁺ T_SCM cells increased in the susceptible group. CON (n = 12), SUS (n = 12), RES (n = 8). ***P < 0.0001 versus the CON group, ^###P < 0.0001 versus the SUS group. Correlations of CD8⁺ T_SCM cell proportions with sucrose uptake in SPT (O) and immobility time in both TST (P) and FST (Q). P < 0.0001 versus the T cell proportions in (O–Q), n = 32. D, E Student’s t test (two-sided). N one-way ANOVA followed by two-sided Holm-Sidak post hoc multiple comparison test. F–M, O–Q two-sided Pearson’s or Spearman’s correlation coefficient. D, E, N Data were presented as mean ± SD. Source data are provided as a Source Data file. pHCs psychiatrically healthy controls, MDD major depressive disorder, T_Naïve cells naïve T cells, T_CM cells central memory T cells, T_EM cells effector memory T cells, T_reg regulatory T cells, T_SCM cells stem cell-like memory T cells, T_EMRA cells terminally differentiated effector memory T cells. HAMD-24 the 24-item Hamilton Depression Rating Scale, MADRS Montgomery Asberg Depression Rating Scale, PHQ-9 the 9-item Patient Health Questionnaire, HAMA Hamilton Anxiety Scale, CON control, SUS susceptible, RES resilient, SPT sucrose preference test, TST tail suspension test, FST forced swim test.