Open AccessPhenotypic characteristics of aged CD 4 + CD 28 null T lymphocytes are determined by changes in the whole‐genome DNA methylation pattern
Author(s) -
SuarezÁlvarez Beatriz,
Rodríguez Ramón M.,
Schlangen Karin,
Raneros Aroa Baragaño,
MárquezKisinousky Leonardo,
Fernández Agustín F.,
DíazCorte Carmen,
Aransay Ana M.,
LópezLarrea Carlos
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12552
Subject(s) - biology , cd28 , dna methylation , epigenetics , gene , t cell , phenotype , cytotoxic t cell , immune system , genetics , gene expression , microbiology and biotechnology , in vitro
Summary Aging is associated with a progressive loss of the CD 28 costimulatory molecule in CD 4 + lymphocytes ( CD 28 null T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole‐genome DNA methylation and gene expression profiles of CD 28 null T cells and its CD 28 + counterpart. A comparative analysis revealed that 296 genes are differentially methylated between the two cell subsets. A total of 160 genes associated with cytotoxicity (e.g. GRZB , TYROBP , and RUNX 3) and cytokine/chemokine signaling (e.g. CX 3 CR 1 , CD 27 , and IL ‐1R ) are demethylated in CD 28 null T cells, while 136 de novo ‐methylated genes matched defects in the TCR signaling pathway (e.g. ITK , TXK , CD 3G , and LCK ). TCR ‐landscape analysis confirmed that CD 28 null T cells have an oligo/monoclonal expansion over the polyclonal background of CD 28 + T cells, but feature a Vβ family repertoire specific to each individual. We reported that CD 28 null T cells show a preactivation state characterized by a higher level of expression of inflammasome‐related genes that leads to the release of IL ‐1β when activated. Overall, our results demonstrate that CD 28 null T cells have a unique DNA methylation landscape, which is associated with differences in gene expression, contributing to the functionality of these cells. Understanding these epigenetic regulatory mechanisms could suggest novel therapeutic strategies to prevent the accumulation and activation of these cells during aging.