Submitted July 26, 2006
Accepted November 22, 2006
Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells
Sanmay Bandyopadhyay, Myrianne Dure, Monika Paroder, Noemi Soto-Nieves, Irene Puga, and Fernando Macian*
Dept of Pathology, Albert Einstein College of Medicine, Bronx, NY, United States
* Corresponding author; email: fmacianj{at}aecom.yu.edu.
In T cells anergy may be evoked by an unbalanced stimulation of the T cell receptor in the absence of costimulation. Anergic T cells are unresponsive to new antigen receptor engagement and do not produce interleukin 2. We present evidence that anergizing stimuli induce changes in histone acetylation, which mediate transcriptional repression of interleukin 2 expression. In response to calcium signaling, anergic T cells upregulate the expression of Ikaros, a zinc finger transcription factor essential for lymphoid lineage determination. Ikaros binds to the interleukin 2 promoter where it induces histone deacetylation. Confirming the role of Ikaros in the induction of T cell anergy, cells with reduced Ikaros activity show defective inactivation in response to an anergizing stimulus. We propose a model in which tolerizing stimuli induce epigenetic changes on the interleukin 2 locus that are responsible for the stable inhibition of the expression of this cytokine in anergic T cells.
