Naive CD4⁺ T cells deficient for IL-12Rβ1 fail to differentiate into IL-21–expressing cells in response to IL-12. (A-F) The frequency of total CD4⁺ T cells, and naive (CD45RA⁺CCR7⁺), memory (CD45RA⁺CCR7^−/+), and CXCR5⁺CD45RA⁻ CD4⁺ T cells, in PBMCs was determined for healthy donors and patients deficient for IL-12Rβ1. (A-B) Representative dot plots from 1 donor and 1 patient. (C-F) The frequency of (C) total, (D) naive (CD45RA⁺CCR7⁺), (E) memory (CD45RA⁺CCR7^−/+), and (F) CXCR5⁺CD45RA⁻ CD4⁺ T cells from all healthy donors (total CD4⁺ T cells, n = 54; naive CD4⁺ T cells, n = 70; memory CD4⁺ T cells, n = 70; CXCR5⁺CD45RA⁻ CD4⁺ T cells, n = 61) and patients deficient for IL-12Rβ1 examined (n = 6). (G-J) Naive CD4⁺ T cells isolated from healthy donors (n = 5) and patients deficient for IL-12Rβ1 (n = 5) were cultured for 5 days under neutral (nil); polarizing Th1, Th2, or Th17 conditions; or in the presence of IL-6, IL-21, IL-23, or IL-27, and intracellular expression of IL-21 and IFNγ were then determined. (G-H) Representative dot plots of IL-21 and IFNγ expression by activated naive CD4⁺ T cells from 1 donor and 1 patient deficient for IL-12Rβ1. (I-J) Percentage of activated normal and IL-12Rβ1–deficient naive CD4⁺ T cells induced to express (I) IL-21 or (J) IFNγ in response to the indicated culture. The values represent the mean ± SEM.