Type I IFN signaling in naïve CD4⁺ T cells in SLE. (a) UMAP visualization of 55,072 peripheral blood CD4⁺ T cells from 11 healthy children and 33 pediatric SLE patients. (b) Scaled expression of T cell lineage genes within clusters shown in a. (c) Proportion of healthy donor or cSLE derived cells in each cluster. (d) Proportion of cluster 6 ISG⁺ cells amongst naïve CD4⁺ T cells across healthy donors and cSLE patients, grouped according to low (SLEDAI ≤ 4) or high (SLEDAI > 4) disease activity. Two patients with an incomplete SLEDAI assessment were excluded from this analysis. (e) Diffusion map visualization of CD4⁺ T cells from an individual cSLE patient (cSLE_27) with high disease activity, colored by their cluster identity. (f) Individual diffusion maps from three representative healthy controls, three representative patients with low disease activity (SLEDAI ≤ 4) or three representative patients with high disease activity (SLEDAI > 4). (g) Diffusion map visualization of CD4⁺ T cells from an individual cSLE patient (cSLE_27) with high disease activity, colored by their expression of T cell lineage genes. (h) Individual diffusion maps (as in f) colored by imputed expression of indicated genes. (i) Palantir pseudotime and branch probabilities illustrating two differentiation trajectories from naïve to T_H1 or T_FH cells. (j) Heatmap showing scaled expression of T cell lineage genes across the naïve and terminal effector memory cell states identified in e. (k and l) Reconstruction of effector T cell differentiation for patient cSLE27. T_H1 branch probability across pseudotime, with cells (dots) colored by cluster identity (k), expression of T cell lineage genes (l). (m) Distribution of expression of mean ISG signature score for each cluster (as in Fig. 4 b) from patient cSLE_27. Cells below the 60th percentile were classified as “ISG-low,” and cells in the top 5% were labeled as “ISG-high.” (n) T_H1 branch probability across pseudotime, with cells (dots) colored by level of ISG expression, for an individual patient, cSLE_27. ISG-low cells adopt a T_H1 effector memory phenotype, whereas high levels of ISG expression are associated with a T_CM or T_FH memory phenotype. (o) T_H1 branch probability across pseudotime, with cells (dots) colored by level of ISG expression, for an individual patient, cSLE_19. Statistical significance determined by Mann–Whitney test (d); *P < 0.05; **P < 0.01.