Figure 3: Frequencies and responses of CD4⁺ T cells from IL-12Rβ1-, IL-12Rβ2- and IL-23R-deficient individuals to polyclonal stimuli or Th-polarizing cytokines.

A) On the left, frequencies of naive (CCR7⁺CD45RA⁺), central memory (CCR7⁺CD45RA⁻), effector memory (CCR7⁻CD45RA⁻) and T_EMRA (CCR7⁻CD45RA⁺) CD4⁺CD3⁺ T cells were measured in healthy controls (n=16), IL-12Rβ2-Q138X patients (n=2, one measured twice), one IL-23R-C115Y patient (technical triplicates) and rL-12Rβ1^−/− patients (n=5). The values shown are the percentage of total CD4⁺ T cells. On the right, frequencies of four subsets of CD4⁺ memory T cells (CD3⁺CD45RA⁻): Th1 (CCR6⁻CCR4⁻CXCR3⁺), Th1* (CCR6⁺CCR4⁻CXCR3⁺), Th17 (CCR6⁺CCR4⁺CXCR3⁻) and Th2 (CCR6⁻CCR4⁺CXCR3⁻) were measured in the same individuals as in the left panel. Error bars indicate the SEM. P values for the comparison of healthy controls with IL-12Rβ1-deficient patients in Mann-Whitney U-tests are shown. Formal statistical comparisons including IL- 12Rβ2-Q138X and IL-23R-C115Y patients were not appropriate, due to the extremely small number of individuals (2 and 1, respectively). B) Naïve CD4⁺ T cells from healthy controls, two IL-12Rβ2-Q138X patients (P1 and P2), one IL-23R-C115Y patient (P4) and four IL- 12Rβ1 -deficient patients were either left unpolarized (Th0) or were polarized under Th1 conditions (TAE+IL-12), Th17 conditions (TAE+IL-1/IL-6/IL-21/IL-23/TGF-β), or Th2 conditions (TAE+IL-4). The production of IFN-γ, IL-17F and IL-10 was measured with cytometric bead arrays, in cell culture supernatants, after 5 days. C) Naïve and memory CD4⁺ T cells from healthy controls, two IL-12Rβ2-Q138X (P1 and P2), one IL- 23R-C115Y (P4) and four IL-12Rβ1-deficient patients were stimulated with TAE beads, and cytokine production was measured 5 days later. Data for the production of IFN-γ, TNF and IL-2 are shown in the upper panels and for IL-17A, IL-17F and IL-10 in the lower panels.