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

✍ Scribed by Thang Nguyen; Ruduan Wang; John H. Russell

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 147 KB
• Volume: 30
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/(sici)1521-4141(200005)30:5<1445::aid-immu1445>3.0.co;2-m

✦ Synopsis

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.