Elucidating how multipotent memory precursor (MP) cells maintain developmental plasticity and longevity to provide long-term immunity while most effector cells develop into terminally differentiated effector (TE) cells with limited survival is necessary for understanding immunological memory formation. We profiled active (H3K27Ac) and repressed (H3K27me3) chromatin states in naïve, MP and TE CD8+ T cells during viral infection, and observed increased H3K27me3 at numerous pro-memory and pro-survival genes in TE relative to MP cells, indicative of fate restriction, but permissive chromatin at both pro-memory and pro-effector genes in MP cells, indicative of multipotency. Deficiency in PRC2-mediated H3K27me3 deposition impaired clonal expansion and TE cell differentiation, but minimally impacted memory cell maturation. Abundant H3K27me3 deposition at pro-memory genes occurred relatively late during TE cell development in a FOXO1-regulated manner. These results outline a detailed temporal model for how effector T cells lose memory cell potential through selective epigenetic-silencing of pro-memory genes.
|School Location:||United States -- Connecticut|
|Source:||DAI-B 78/07(E), Dissertation Abstracts International|
|Keywords:||CD8+ T Cell, Differentiation, EZH2, Epigenetics, H3K27me3, Polycomb|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be