Mature T Cells Depend on Signaling through the IKK Complex

AbstractThe transcription factor NF-κB is implicated in various aspects of T cell development and function. The IκB kinase (IKK) complex, consisting of two kinases, IKK1/α and IKK2/β, and the NEMO/IKKγ regulatory subunit, mediates NF-κB activation by most known stimuli. Adoptive transfer experiments had demonstrated that IKK1 and IKK2 are dispensable for T cell development. We show here that T lineage-specific deletion of IKK2 allows survival of naive peripheral T cells but interferes with the generation of regulatory and memory T cells. T cell-specific ablation of NEMO or replacement of IKK2 with a kinase-dead mutant prevent development of peripheral T cells altogether. Thus, IKK-induced NF-κB activation, mediated by either IKK1 or IKK2, is essential for the generation and survival of mature T cells, and IKK2 has an additional role in regulatory and memory T cell development