Mature T Cells Depend on Signaling through the IKK Complex
pmid: 14499113
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.
- Harvard University United States
- National Institute for Nuclear Physics Italy
- University of Cologne Germany
- Millennium Pharmaceuticals United States
- Institut Pasteur France
Mice, Knockout, Integrases, T-Lymphocytes, Immunology, NF-kappa B, Protein Serine-Threonine Kinases, I-kappa B Kinase, Mice, Viral Proteins, Infectious Diseases, CD4 Antigens, Immunology and Allergy, Animals, Cell Division, Signal Transduction
Mice, Knockout, Integrases, T-Lymphocytes, Immunology, NF-kappa B, Protein Serine-Threonine Kinases, I-kappa B Kinase, Mice, Viral Proteins, Infectious Diseases, CD4 Antigens, Immunology and Allergy, Animals, Cell Division, Signal Transduction
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