Abstract:
:T cell activation involves the orchestration of several signaling pathways, including that of the 'classical' transcription factor NF-kappaB components NF-kappaB1-RelA. The function of the 'nonclassical' NF-kappaB2-RelB pathway is less clear, although T cells lacking components of this pathway have activation defects. Here we show that mice deficient in NF-kappaB-inducing kinase have a complex phenotype consisting of immunosuppression mediated by CD25(-)Foxp3(-) memory CD4(+) cells and, in the absence of those cells, hyper-responsive naive CD4(+) T cells, which caused autoimmune lesions after adoptive transfer into hosts deficient in recombination-activating genes. Biochemical studies indicated involvement of a cell-intrinsic mechanism in which NF-kappaB2 (p100) limits nuclear translocation of NF-kappaB1-RelA and thereby functions as a regulatory 'brake' for the activation of naive T cells.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Ishimaru N,Kishimoto H,Hayashi Y,Sprent Jdoi
10.1038/ni1351subject
Has Abstractpub_date
2006-07-01 00:00:00pages
763-72issue
7eissn
1529-2908issn
1529-2916pii
ni1351journal_volume
7pub_type
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