Regulation of naive T cell function by the NF-kappaB2 pathway.
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.
Ishimaru
Naozumi
N
The Scripps Research Institute, La Jolla, California 92037, USA.
Kishimoto
Hidehiro
H
Hayashi
Yoshio
Y
Sprent
Jonathan
J
D021581:Active Transport, Cell Nucleus; D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured / Q000166:cytology / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency; D051858:Forkhead Transcription Factors / Q000032:analysis; D005786:Gene Expression Regulation; D018960:Hyaluronan Receptors / Q000032:analysis; D007156:Immunologic Memory / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency; D051996:Transcription Factor RelA / Q000378:metabolism; D051841:Transcription Factor RelB / Q000172:deficiency / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D017346:Protein Serine-Threonine Kinases; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D000097782:NF-kappaB-Inducing Kinase; C476399:Cd44 protein, mouse; C498833:Foxp3 protein, mouse; C499308:Rag2 protein, mouse; C498144:Rela protein, mouse; C497594:Relb protein, mouse; C073701:Nfkb1 protein, mouse