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Immunity. 2013 Oct 17;39(4):661-75. doi: 10.1016/j.immuni.2013.08.032. Epub 2013 Oct 10.

Epigenetic modifications induced by Blimp-1 Regulate CD8⁺ T cell memory progression during acute virus infection.

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  • 1Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Abstract

The transcription factor Blimp-1 regulates the overall accumulation of virus-specific CD8⁺ T cells during acute viral infections. We found that increased proliferation and survival of Blimp-1-deficient CD8⁺ T cells resulted from sustained expression of CD25 and CD27 and persistent cytokine responsiveness. Silencing of Il2ra and Cd27 reduced the Blimp-1-deficient CD8⁺ T cell response. Genome-wide chromatin immunoprecipitation (ChIP) sequencing analysis identified Il2ra and Cd27 as direct targets of Blimp-1. At the peak of the antiviral response, but not earlier, Blimp-1 recruited the histone-modifying enzymes G9a and HDAC2 to the Il2ra and Cd27 loci, thereby repressing expression of these genes. In the absence of Blimp-1, Il2ra and Cd27 exhibited enhanced histone H3 acetylation and reduced histone H3K9 trimethylation. These data elucidate a central mechanism by which Blimp-1 acts as an epigenetic regulator and enhances the numbers of short-lived effector cells while suppressing the development of memory-precursor CD8⁺ T cells.

Copyright © 2013 Elsevier Inc. All rights reserved.

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