Ruduan Wang

IL-12 enhances IL-2 function by inducing CD25 expression through a p38 mitogen-activated protein kinase pathway.

We previously showed that an IL‐2 mutant, Q126D, could induce T cells to proliferate to the same extent as wild‐type IL‐2 but was unable to sensitize T cells to activation‐induced cell death (AICD). Here we show that the partial signaling of Q126D is attributable to its inability to up‐regulate the IL‐2 receptor alpha chain (CD25). IL‐12, which can up‐regulate CD25 expression, enhances the ability of Q126D to induce AICD sensitivity and proliferation. IL‐12 synergism with Q126D is dependent on CD25 up‐regulation because the synergism is absent in CD25‐deficient T cells. Inhibition of IL‐12‐induced up‐regulation of CD25 by a p38 mitogen‐activated protein (MAP) kinase inhibitor, SB203580, also ablates the synergism between IL‐12 and Q126D. Although CD25 is important for IL‐2‐induced proliferation and AICD sensitivity, it is not absolutely required because a high concentration of IL‐2 can overcome the requirement for CD25. Under physiological concentrations of IL‐2, CD25 expression is critical for the function of IL‐2. IL‐12 can enhance the function of IL‐2 by up‐regulating CD25 in a p38 MAP kinase‐dependent manner.