IL-21 can substitute for IL-2 in conventional, but not regulatory, T cells. (A) BALB/c CD4+CD25− Tconv (2.5 × 104) were cultured with anti-CD3 and 5 × 104 CD19+ B cells alone, with anti–IL-2 antibody, or with both anti–IL-2 Ab and 200 ng/mL IL-21. Relative Tconv cell counts are shown at day 3. The average Tconv cell number in the absence of cytokine or Tregs was 94 497 ± 8704. (B) BALB/c CD4+CD25+ Tregs (2.5 × 104) were cultured alone or in the presence of either 20 ng/mL IL-2 or 200 ng/mL IL-21. Representative staining for Foxp3 and CD25 and relative cell counts are shown at day 3. Data are representative of at least 3 independent experiments. **P < .01; ***P < .001. ns indicates not significant.