Abstract
T cell activation involves the orchestration of several signaling pathways, including that of the 'classical' transcription factor NF-κB components NF-κB1–RelA. The function of the 'nonclassical' NF-κB2–RelB pathway is less clear, although T cells lacking components of this pathway have activation defects. Here we show that mice deficient in NF-κB-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-κB2 (p100) limits nuclear translocation of NF-κB1–RelA and thereby functions as a regulatory 'brake' for the activation of naive T cells.
NOTE: In the version of this article initially published, the sentence on page 763, column 2, line 12 is incorrect. The correct sentence should end “…and these mice show increased susceptibility to typhlocolitis and infection with Leishmania major but are resistant to experimental autoimmune encephalomyelitis and asthma14–17.” The error has been corrected in the PDF version of the article.
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Change history
19 October 2007
In the version of this article initially published, the legends for Figures 1 and 5 are incorrect. The correct phrasing should be, for Figure 1a, “... injection of α-DEC-MCC, α-DEC-APL constructs, α-DEC-ovalbumin (α-DEC-OVA), α-DEC-205 plus isotype-MCC (α-DEC + iso-MCC) or PBS...”; for Figure 1b,c, “...injection of α-DEC-MCC, α-DEC-APL constructs, α-DEC-ovalbumin, α-DEC-205 plus isotype-MCC or PBS...”; and for Figure 5, “...mice were injected with α-DEC-APL constructs and then, 5 h later, with Fluo-4 AM– and CMRA-colabeled AND T cells” on line 2, and ‘Frequency of AND T cells with ‘sustained’ Ca2+ increase in mice treated...” on line 3. The errors have been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank B. Marchand for typing the manuscript. Supported by the United States Public Health Service (CA38355, AI21487, AI46710 and AG01743; publication number 17327-IMM from The Scripps Research Institute) and by the Ministry of Education, Science, and Culture of Japan (grants-in-aid for scientific research; 17689049).
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Supplementary information
Supplementary Fig. 1
Proliferation of T cell subsets. (PDF 428 kb)
Supplementary Fig. 2
Suppressive effect of aly/aly memory CD4+ T cells. (PDF 214 kb)
Supplementary Fig. 3
Expression of Foxp3 in CD4+ cell subsets. (PDF 92 kb)
Supplementary Fig. 4
Comparison of memory CD4+ and CD25+CD4+ cells. (PDF 183 kb)
Supplementary Fig. 5
NF-κB1/NF-κB2 association. (PDF 185 kb)
Supplementary Fig. 6
Immunoblots for NF-κB subunits in Jurkat or A431 cell lysates. (PDF 71 kb)
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Ishimaru, N., Kishimoto, H., Hayashi, Y. et al. Regulation of naive T cell function by the NF-κB2 pathway. Nat Immunol 7, 763–772 (2006). https://doi.org/10.1038/ni1351
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DOI: https://doi.org/10.1038/ni1351
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