Induction of IL-10 by Th2- and Th17-polarizing cultures is compromised by mutations in IL21R and STAT3. (A and B) Naive CD4⁺ T cells from healthy donors were cultured with TAE beads alone (Th0) or under Th1, Th2, or Th17 conditions for 5 d. After this time, the cells were harvested and analyzed for IL-10 production by intracellular staining and flow cytometry (A; n = 15) or CBA (n = 24). Values represent mean ± SEM. ****, P < 0.0001 compared with Th0 (ANOVA). (C and D) Naive CD4⁺ T cells from healthy donors or patients were cultured with TAE beads alone (Th0) or under Th2 (C) or Th17 (D) conditions for 5 d. IL-10 secretion was determined by CBA. Values represent mean ± SEM; dashed line indicates the mean level of IL-10 secretion under Th0 conditions. Controls, n = 31–35; STAT3_DN, n = 6–8; STAT1_GOF, n = 8; STAT1_LOF, n = 4–5; IL21R, n = 4–5; IL10R, n = 1–2; CD40LG, n = 5; NEMO, n = 2–3; BTK, n = 7; ICOS, n = 3; IL12RB1, n = 5–6; IFNGR1, n = 2–5; TYK2, n = 2–3. **, P < 0.01; ***, P < 0.001, compared with controls (ANOVA; Student’s t test).