NDLI: Early Growth Response Gene-2, a Zinc-Finger Transcription Factor, Is Required for Full Induction of Clonal Anergy in CD4+ T Cells

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Early Growth Response Gene-2, a Zinc-Finger Transcription Factor, Is Required for Full Induction of Clonal Anergy in CD4+ T Cells

Content Provider	Scilit
Author	Harris, John E. Bishop, Kenneth D. Phillips, Nancy E. Mordes, John P. Greiner, Dale L. Rossini, Aldo A. Czech, Michael P.
Copyright Year	2004
Description	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.
Ending Page	7338
Page Count	8
Starting Page	7331
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.173.12.7331
Alternate Webpage(s)	http://www.jimmunol.org/content/173/12/7331.full.pdf
Journal	The Journal of Immunology
Issue Number	12
Volume Number	173
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2004-12-15
Access Restriction	Open
Subject Keyword	Transcription Factor Cultured T Cells Small Interfering Rna Gene Expression Full Induction Response Gene
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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