Title

Early growth response gene-2, a zinc-finger transcription factor, is required for full induction of clonal anergy in CD4+ T cells

UMMS Affiliation

Program in Molecular Medicine; Department of Medicine, Division of Diabetes; Department of Medicine, Division of Endocrinology and Metabolism

Date

12-9-2004

Document Type

Article

Subjects

Animals; Antigens, CD28; Antigens, CD3; CD4-Positive T-Lymphocytes; Cell Line; Cell Proliferation; Clonal Anergy; Clone Cells; DNA-Binding Proteins; inhibitors; Early Growth Response Protein 2; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation; Gene Silencing; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Phosphorylation; RNA, Small Interfering; Receptors, Antigen, T-Cell; Transcription Factors; inhibitors; Up-Regulation; Zinc Fingers

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Ag-specific immune tolerance results from the induction of cellular mechanisms that limit T cell responses to selective Ags. One of these mechanisms is characterized by attenuated proliferation and decreased IL-2 production in fully stimulated CD4(+) Th cells and is denoted T cell anergy. We report the identification of the early growth response gene (Egr-2; Krox-20), a zinc-finger transcription factor, as a key protein required for induction of anergy in cultured T cells. Gene array screening revealed high Egr-2 expression distinctly persists in anergized but not proliferating murine A.E7 T cells. In contrast, Egr-1, a related family member induced upon costimulation, displays little or no expression in the anergic state. IL-2-mediated abrogation of anergy causes rapid depletion of Egr-2 protein. Full stimulation of anergic A.E7 T cells fails to enhance IL-2 and Egr-1 expression, whereas Egr-2 expression is greatly increased. Silencing Egr-2 gene expression by small interfering RNA treatment of cultured A.E7 T cells before incubation with anti-CD3 alone prevents full induction of anergy. However, small interfering RNA-mediated depletion of Egr-2 5 days after anergy induction does not appear to abrogate hyporesponsiveness to stimulation. These data indicate that sustained Egr-2 expression is necessary to induce a full anergic state through the actions of genes regulated by this transcription factor.

Rights and Permissions

Citation: J Immunol. 2004 Dec 15;173(12):7331-8.

Related Resources

Link to Article in PubMed

PubMed ID

15585857