Mature T cells depend on signaling through the IKK complex

Immunity. 2003 Sep;19(3):377-89. doi: 10.1016/s1074-7613(03)00237-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / genetics
  • Cell Division / physiology
  • I-kappa B Kinase
  • Integrases / genetics
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction / immunology*
  • T-Lymphocytes / metabolism*
  • Viral Proteins / genetics

Substances

  • CD4 Antigens
  • NF-kappa B
  • Viral Proteins
  • Protein-Serine-Threonine Kinases
  • Chuk protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse
  • Ikbke protein, mouse
  • Cre recombinase
  • Integrases