Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling

Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-κB and interferon (IFN) signaling. Mice lacking the IKK kinase TAK1 underwent normal positive selection, but exhibited a specific block in functional maturation. NF-κB signaling provided protection from tumor necrosis factor (TNF) mediated death, and was required for proliferation and emigration. The interferon signature was independent of NF-κB, however IFN-αR–deficient thymocytes showed reduced STAT1 expression and phenotypic abnormality, but were competent to proliferate. Thus, both NF-κB and tonic IFN signals are involved in the final maturation of thymocytes into naïve T cells.