ArticleProceedings of the National Academy of Sciences of the United States of America1996
In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 112 citations in OpenAlex.
- Resolving ScRNA-Seq Signatures of Antigen-Specific CD4bioRxiv : the preprint server for biology · 2025Article
- Transcription factors early growth response gene (Egr) 2 and 3 control inflammatory responses of tolerant T cells.Immunity, inflammation and disease · 2018Article
- TGFβ-dependent expression of PD-1 and PD-L1 controls CD8(+) T cell anergy in transplant tolerance.eLife · 2016Article
- Stable Phenotypic Changes of the Host T Cells Are Essential to the Long-Term Stability of Latent HIV-1 Infection.Journal of virology · 2015Article
- Article
- Memory T cells in the chronic inflammatory microenvironment of nasal polyposis are hyporesponsive to signaling through the T cell receptor.Journal of the Association for Research in Otolaryngology : JARO · 2012Article
- Anergic CD8+ T lymphocytes have impaired NF-κB activation with defects in p65 phosphorylation and acetylation.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Analysis of sirtuin 1 expression reveals a molecular explanation of IL-2-mediated reversal of T-cell tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Dynamic palmitoylation and the role of DHHC proteins in T cell activation and anergy.Advances in immunology · 2011Review
- The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell-mediated peripheral T cell unresponsiveness.Nature immunology · 2010Article
- Article
- Tolerance induced via TLR2 and TLR4 in human dendritic cells: role of IRAK-1.BMC immunology · 2008Article
- Molecular mechanisms for adaptive tolerance and other T cell anergy models.Seminars in immunology · 2007Review
- Persistent antigenic stimulation alters the transcription program in T cells, resulting in antigen-specific tolerance.European journal of immunology · 2006Article
- IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508.The Journal of experimental medicine · 2005Article
- Regulation of the maintenance of peripheral T-cell anergy by TAB1-mediated p38 alpha activation.Molecular and cellular biology · 2004Article
- PKCtheta signals activation versus tolerance in vivo.The Journal of experimental medicine · 2004Article
- Identification of the genes specifically expressed in orally tolerized T cells.Cytotechnology · 2003Article
- Staphylococcal enterotoxin H contrasts closely related enterotoxins in species reactivity.Immunology · 2002Article
- Anergy in peripheral memory CD4(+) T cells induced by low avidity engagement of T cell receptor.The Journal of experimental medicine · 2001Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anergy is a major mechanism to ensure antigen-specific tolerance in T lymphocytes in the adult. In vivo, anergy has mainly been studied at the cellular level. In this study, we used the T-cell-activating superantigen staphylococcal enterotoxin A (SEA) to investigate molecular mechanisms of T-lymphocyte anergy in vivo. Injection of SEA to adult mice activates CD4+ T cells expressing certain T-cell receptor (TCR) variable region beta-chain families and induces strong and rapid production of interleukin 2 (IL-2). In contrast, repeated injections of SEA cause CD4+ T-cell deletion and anergy in the remaining CD4+ T cells, characterized by reduced expression of IL-2 at mRNA and protein levels. We analyzed expression of AP-1, NF-kappa B, NF-AT, and octamer binding transcription factors, which are known to be involved in the regulation of IL-2 gene promoter activity. Large amounts of AP-1 and NF-kappa B and significant quantities of NF-AT were induced in SEA-activated CD4+ spleen T cells, whereas Oct-1 and Oct-2 DNA binding activity was similar in both resting and activated T cells. In contrast, anergic CD4+ T cells contained severely reduced levels of AP-1 and Fos/Jun-containing NF-AT complexes but expressed significant amounts of NF-kappa B and Oct binding proteins after SEA stimulation. Resolution of the NF-kappa B complex demonstrated predominant expression of p50-p65 heterodimers in activated CD4+ T cells, while anergic cells mainly expressed the transcriptionally inactive p50 homodimer. These alterations of transcription factors are likely to be responsible for repression of IL-2 in anergic T cells.
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