Regulatory T Cells Suppress Expression of IL-2 by Responder T Cells via a Transcriptional Mechanism (136.40)

Autor: Rita J Luther, David Randolph, Jessy Deshane, Craig Maynard, Karen Janowski, Jimmy Oliver, Casey T Weaver
Rok vydání: 2009
Předmět:
Zdroj: The Journal of Immunology. 182:136.40-136.40
ISSN: 1550-6606
0022-1767
Popis: Interleukin-2 (IL-2) is a type I cytokine that undergoes transcriptional activation downstream of T-cell receptor engagement and CD28 co-stimulation. IL-2 has been shown to have a role in self-tolerance as the presence of this cytokine, shown in several mouse models, necessitates the presence of a sufficient population of T regulatory cells (T reg). Tregs have a critical role in limiting the development of autoreactive effector T cells from naïve precursors that have escaped negative selection within the thymus. Ongoing studies indicate several mechanisms by which Tregs suppress induction of effector T cell responses, one of which is the inhibition of IL-2 gene expression. While several studies have indicated an inhibition of IL-2 mRNA and protein expression by responder CD4+ T cells co-cultured with T regs, the mechanism (s) remains unclear, although effects on both IL-2 gene transcription and mRNA stability have been implicated. In order to examine transcriptional and post-transcriptional effects on IL-2 expression, we have generated an IL-2 BAC-in transgenic reporter mouse model, 2BiT, in which a Thy1.l reporter is expressed under control of the extended Il2 locus. Herein we show that the Thy1.1 IL-2 reporter is expressed with fidelity to the endogenous IL-2 genes. Co-culture assays indicate that transcriptional activation of the reporter in responder T cells is inhibited in the presence of T regs, despite modest effects on IL-2 mRNA half-life (t1/2). These findings indicate that T regulatory cells suppress IL-2 expression primarily through inhibition of transcription rather than modulation of IL-2 mRNA stability.
Databáze: OpenAIRE
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