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Regulation of naive T cell function by the NF-κB2 pathway

Nature Immunology volume 7, pages 763–772 (2006)Cite this article

A Corrigendum to this article was published on 01 November 2007

This article has been updated

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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Figure 1: NF-κB activation in CD4+ T cells.
Figure 2: T cell responses of mice deficient in NF-κB2–RelB.
Figure 3: IL-2 secretion and IL-2R synthesis by aly/aly CD4+ subsets.
Figure 4: Proliferative responses of naive and memory aly/aly CD4+ subsets in vivo.
Figure 5: Molecular interactions between NF-κB subunits during T cell activation.
Figure 6: Kinetics of NF-κB1 and NF-κB2 expression in naive CD4+ cells after TCR ligation.
Figure 7: Induction of autoimmune disease by subsets of aly/+ and aly/aly CD4+ cells.

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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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Authors and Affiliations

  1. The Scripps Research Institute, La Jolla, 92037, California, USA

    Naozumi Ishimaru & Jonathan Sprent

  2. Department of Oral Molecular Pathology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8504, Japan

    Naozumi Ishimaru & Yoshio Hayashi

  3. Research Institute for Biological Sciences, Tokyo University of Science, Noda-City, 278-0022, Chiba, Japan

    Hidehiro Kishimoto

  4. Garvan Institute of Medical Research, Darlinghurst, 2010, NSW, Australia

    Jonathan Sprent

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Correspondence to Jonathan Sprent.

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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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