Mature T cells depend on signaling through the IKK complex.
The transcription factor NF-kappaB is implicated in various aspects of T cell development and function. The IkappaB kinase (IKK) complex, consisting of two kinases, IKK1/alpha and IKK2/beta, and the NEMO/IKKgamma regulatory subunit, mediates NF-kappaB 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-kappaB 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.
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D051550:I-kappa B Kinase; D019426:Integrases / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics
D015704:CD4 Antigens; D016328:NF-kappa B; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; C045073:Cre recombinase; D019426:Integrases