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

Meredith Safford, Samuel Lester Collins, Michael A. Lutz, Amy Allen, Ching Tai Huang, Jeanne Kowalski, Amanda Blackford, Maureen Horton, Charles Drake, Ronald H. Schwartz, Jonathan Powell

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)472-480
Number of pages9
JournalNature Immunology
Volume6
Issue number5
DOIs
StatePublished - 2005

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T-Lymphocytes
Ubiquitin-Protein Ligases
Growth
T-Cell Antigen Receptor
Genes
Microarray Analysis
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Egr-2 and Egr-3 are negative regulators of T cell activation. / Safford, Meredith; Collins, Samuel Lester; Lutz, Michael A.; Allen, Amy; Huang, Ching Tai; Kowalski, Jeanne; Blackford, Amanda; Horton, Maureen; Drake, Charles; Schwartz, Ronald H.; Powell, Jonathan.

In: Nature Immunology, Vol. 6, No. 5, 2005, p. 472-480.

Research output: Contribution to journalArticle

Safford, M, Collins, SL, Lutz, MA, Allen, A, Huang, CT, Kowalski, J, Blackford, A, Horton, M, Drake, C, Schwartz, RH & Powell, J 2005, 'Egr-2 and Egr-3 are negative regulators of T cell activation', Nature Immunology, vol. 6, no. 5, pp. 472-480. https://doi.org/10.1038/ni1193
Safford M, Collins SL, Lutz MA, Allen A, Huang CT, Kowalski J et al. Egr-2 and Egr-3 are negative regulators of T cell activation. Nature Immunology. 2005;6(5):472-480. https://doi.org/10.1038/ni1193
Safford, Meredith ; Collins, Samuel Lester ; Lutz, Michael A. ; Allen, Amy ; Huang, Ching Tai ; Kowalski, Jeanne ; Blackford, Amanda ; Horton, Maureen ; Drake, Charles ; Schwartz, Ronald H. ; Powell, Jonathan. / Egr-2 and Egr-3 are negative regulators of T cell activation. In: Nature Immunology. 2005 ; Vol. 6, No. 5. pp. 472-480.
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