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Title: Persistent antigenic stimulation alters the transcription program in T cells, resulting in antigen-specific tolerance.
Authors: Anderson, PO
Manzo, BA
Sundstedt, A
Minaee, S
Symonds, A
Khalid, S
Rodriguez-Cabezas, ME
Nicolson, K
Li, S
Wraith, DC
Wang, P
Keywords: Animals
Cell cycle
Cell nucleus
Cyclin-dependent kinase inhibitor p21
Cyclin-dependent kinase inhibitor p27
Early growth response protein 2
Epitopes, T-Lymphocyte
Gene expression profiling
Gene expression regulation
Immune tolerance
Lymphocyte activation
Mice, transgenic
Oligonucleotide array sequence analysis
Reverse transcriptase polymerase chain reaction
Signal transduction
T-box domain proteins
T-Lymphocytes, Regulatory
Transcription factors
Transcription, Genetic
Publication Date: 2006
Publisher: Wiley-Blackwell
Citation: European Journal of Immunology 36(6): 1374 - 1385, Jun 2006
Abstract: Repetitive antigen stimulation induces peripheral T cell tolerance in vivo. It is not known, however, whether multiple stimulations merely suppress T cell activation or, alternatively, change the transcriptional program to a distinct, tolerant state. In this study, we have discovered that STAT3 and STAT5 were activated in response to antigen stimulation in vivo, in marked contrast to the suppression of AP-1, NF-kappaB and NFAT. In addition, a number of transcription factors were induced in tolerant T cells following antigen challenge in vivo, including T-bet, Irf-1 and Egr-2. The altered transcription program in tolerant cells associates closely with the suppression of cell cycle progression and IL-2 production, as well as with the induction of IL-10. Studies of T-bet and Egr-2 show that the function of T-bet in peptide treatment-induced regulatory T cells is not associated with Th1 differentiation, but correlates with the suppression of IL-2, whereas expression of Egr-2 led to an up-regulation of the cell cycle inhibitors p21(cip1) and p27(kip). Our results demonstrate a balanced transcription program regulated by different transcription factors for T cell activation and/or tolerance during antigen-induced T cell responses. Persistent antigen stimulation can induce T cell tolerance by changing the balance of transcription factors.
Description: This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2006 Wiley-Blackwell.
Sponsorship: This work was supported by a Programme Grant from the Wellcome Trust, Swedish Strategic Research fund, Barts Foundation for Research Limited and Brunel University.
ISSN: 0014-2980
Appears in Collections:Biological Sciences
Dept of Life Sciences Research Papers

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