Essential role for IKKgamma/NEMO in TCR-induced IL-2 expression in Jurkat T cells.

The control of IL-2 gene expression in T cells by multiple transcriptional factors has been extensively explored, however, the role of the NF-kappaB signaling pathway in TCR-dependent IL-2 production still remains unclear. In this study, we used a somatic cell genetics approach to address this question. Triggering TCR in mutant Jurkat T cells lacking IKKgamma/NEMO failed to induce IL-2 due to a selective loss in I-kappaB kinase activity, I-kappaBalpha degradation and NF-kappaB DNA-binding activity. The AP-1 and NF-AT binding activities in the IL-2 promoter were comparable between wild-type and mutant T cells. These defects in the mutant cell line were rescued by the reintroduction of exogenous IKKgamma. Taken together, our data demonstrate that IKKgamma plays an essential role in TCR-induced signaling pathways leading to IL-2 expression.