Defective Transcription of the IL-2 Gene Is Associated with Impaired Expression of c-Fos, FosB, and JunB in Anergic T Helper 1 Cells

Anna Mondino, Carmella D. Whaley, Dimuthu R. DeSilva, Wei Li, Marc K. Jenkins, Daniel L. Mueller

Research output: Contribution to journalArticle

Abstract

Anergic CD4+ Th cells do not produce IL-2 when challenged with Ag-pulsed accessory cells because of a transcriptional defect. In this work, we report that these anergic T cells are defective in their ability to up-regulate protein binding and transactivation at two critical IL-2 DNA enhancer elements: NF-AT (nuclear factor of activated T cells; a sequence that binds a heterotrimeric NFATp, Fos, and Jun protein complex) and Activator Protein-1 (AP-1) (that binds Fos and Jun heterodimers). Western blot analysis of nuclear extracts showed that the impaired DNA-protein interactions in anergic T cells were associated with poor expression of the inducible AP-1 family members c-Fos, FosB, and JunB. However, the reduced expression of these proteins was not the result of a global TCR/CD3-signaling defect because CD3 cross-linking induced an equivalent increase in intracellular-free calcium ions, as well as NFATp dephosphorylation, translocation to the nucleus, and DNA binding in both normal and anergic T cells. Thus, defective IL-2 gene transcription appears to be due, at least in part, to a selective block in the expression of the AP-1 Fos and Jun family members in anergic T cells.

Original languageEnglish
Pages (from-to)2048-2057
Number of pages10
JournalJournal of Immunology
Volume157
Issue number5
Publication statusPublished - Sep 1 1996

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Th1 Cells
Interleukin-2
Transcription Factor AP-1
T-Lymphocytes
Genes
DNA
NFATC Transcription Factors
Proteins
Aptitude
Protein Binding
Transcriptional Activation
Up-Regulation
Western Blotting
Ions
Calcium

ASJC Scopus subject areas

  • Immunology

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Defective Transcription of the IL-2 Gene Is Associated with Impaired Expression of c-Fos, FosB, and JunB in Anergic T Helper 1 Cells. / Mondino, Anna; Whaley, Carmella D.; DeSilva, Dimuthu R.; Li, Wei; Jenkins, Marc K.; Mueller, Daniel L.

In: Journal of Immunology, Vol. 157, No. 5, 01.09.1996, p. 2048-2057.

Research output: Contribution to journalArticle

Mondino, Anna ; Whaley, Carmella D. ; DeSilva, Dimuthu R. ; Li, Wei ; Jenkins, Marc K. ; Mueller, Daniel L. / Defective Transcription of the IL-2 Gene Is Associated with Impaired Expression of c-Fos, FosB, and JunB in Anergic T Helper 1 Cells. In: Journal of Immunology. 1996 ; Vol. 157, No. 5. pp. 2048-2057.
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AB - Anergic CD4+ Th cells do not produce IL-2 when challenged with Ag-pulsed accessory cells because of a transcriptional defect. In this work, we report that these anergic T cells are defective in their ability to up-regulate protein binding and transactivation at two critical IL-2 DNA enhancer elements: NF-AT (nuclear factor of activated T cells; a sequence that binds a heterotrimeric NFATp, Fos, and Jun protein complex) and Activator Protein-1 (AP-1) (that binds Fos and Jun heterodimers). Western blot analysis of nuclear extracts showed that the impaired DNA-protein interactions in anergic T cells were associated with poor expression of the inducible AP-1 family members c-Fos, FosB, and JunB. However, the reduced expression of these proteins was not the result of a global TCR/CD3-signaling defect because CD3 cross-linking induced an equivalent increase in intracellular-free calcium ions, as well as NFATp dephosphorylation, translocation to the nucleus, and DNA binding in both normal and anergic T cells. Thus, defective IL-2 gene transcription appears to be due, at least in part, to a selective block in the expression of the AP-1 Fos and Jun family members in anergic T cells.

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