Epigenetic Modifications Induced by Blimp-1 Regulate CD8(+) T Cell Memory Progression during Acute Virus Infection
Immunology & Virology Program
Department of Pathology
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.
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Citation: Shin HM, Kapoor VN, Guan T, Kaech SM, Welsh RM, Berg LJ. Epigenetic Modifications Induced by Blimp-1 Regulate CD8(+) T Cell Memory Progression during Acute Virus Infection. Immunity. 2013 Oct 17;39(4):661-75. doi: 10.1016/j.immuni.2013.08.032. Link to article on publisher's website