[PDF][PDF] Mature T cells depend on signaling through the IKK complex

M Schmidt-Supprian, G Courtois, J Tian, AJ Coyle… - Immunity, 2003 - cell.com
M Schmidt-Supprian, G Courtois, J Tian, AJ Coyle, A Israël, K Rajewsky, M Pasparakis
Immunity, 2003cell.com
The 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 …
Abstract
The 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.
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