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Egr-2 and Egr-3 are negative regulators of T cell activation

Nature Immunology volume 6, pages 472–480 (2005)Cite this article

An Erratum to this article was published on 01 July 2005

Abstract

T cell receptor engagement in the absence of proper accessory signals leads to T cell anergy. E3 ligases are involved in maintaining the anergic state. However, the specific molecules responsible for the induction of anergy have yet to be elucidated. Using microarray analysis we have identified here early growth response gene 2 (Egr-2) and Egr-3 as key negative regulators of T cell activation. Overexpression of Egr2 and Egr3 was associated with an increase in the E3 ubiquitin ligase Cbl-b and inhibition of T cell activation. Conversely, T cells from Egr3−/− mice had lower expression of Cbl-b and were resistant to in vivo peptide-induced tolerance. These data support the idea that Egr-2 and Egr-3 are involved in promoting a T cell receptor–induced negative regulatory genetic program.

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Figure 1: Gene chip analysis of T cells stimulated in conditions that promote and inhibit anergy.
Figure 2: Differential expression of Egr family members.
Figure 3: Differential expression of Egr2 and Egr3.
Figure 4: In vivo expression of Egr2 and Egr3 during tolerance induction.
Figure 5: Overexpression of Egr2 and Egr3 inhibits T cell function.
Figure 6: Egr3−/− T cells are resistant to peptide-induced tolerance in vivo.
Figure 7: Egr2 and Egr3 influence Cbl-b expression.

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Acknowledgements

We thank B. Majane (National Institutes of Health, Bethesda, Maryland) for help in breeding and maintaining the mouse lines; C. Chen and L. Luu for technical assistance; and D.M. Pardoll (Johns Hopkins University, Baltimore, Maryland) for critical review of the manuscript. Supported by the National Cancer Institute (R01CA098109-02).

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Author notes

  1. Meredith Safford, Samuel Collins and Michael A Lutz: These authors contributed equally to this work.

Authors and Affiliations

  1. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Meredith Safford, Samuel Collins, Michael A Lutz, Amy Allen, Jeanne Kowalski, Amanda Blackford, Charles Drake & Jonathan D Powell

  2. Chang Gung University School of Medicine and Hospital, Taiwan, China

    Ching-Tai Huang

  3. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Maureen R Horton

  4. Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Ronald H Schwartz

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Correspondence to Jonathan D Powell.

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Supplementary information

Supplementary Fig. 1

Potential anergic networks. (PDF 593 kb)

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Safford, M., Collins, S., Lutz, M. et al. Egr-2 and Egr-3 are negative regulators of T cell activation. Nat Immunol 6, 472–480 (2005). https://doi.org/10.1038/ni1193

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