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

Eur J Immunol. 2000 May;30(5):1445-52. doi: 10.1002/(SICI)1521-4141(200005)30:5<1445::AID-IMMU1445>3.0.CO;2-M.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Drug Synergism
  • Interleukin-12 / immunology*
  • Interleukin-12 / pharmacology
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology*
  • Interleukin-2 / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinases / immunology*
  • Mutation
  • Receptors, Interleukin-2 / immunology*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • p38 Mitogen-Activated Protein Kinases


  • Interleukin-2
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Interleukin-12
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases