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CUTTING EDGE |
Promoter Demethylation in CD44highCD8+ T Lymphocytes1
Leukocyte Biology Unit of the Queensland Institute of Medical Research and the Joint Transplantation Biology Program of the University of Queensland, Brisbane, Australia
Genomic DNA methylation patterns influence the development and
maintenance of function during cellular differentiation. Methylation of
regulatory sequences can have long-lasting effects on gene expression
if inherited in an epigenetic manner. Recent work suggests that DNA
methylation has a regulatory role in differential cytokine gene
expression in primary T lymphocytes. Here we show, by clonal lineage
analysis, that methylation patterns in the IFN-
promoter exhibit
long term faithful inheritance in CD44highCD8+
T cells and their progeny, through 16 cell divisions and a clonal
expansion of 5 orders of magnitude. Moreover, the demethylated IFN-
promoter is faithfully inherited following the withdrawal of T cell
stimulation and the loss of detectable IFN- mRNA, consistent with
passive rather than active maintenance mechanisms. This represents a
form of stable cellular memory, of defined epigenetic characteristics,
that may contribute to the maintenance of T cell cytokine expression
patterns and T cell memory.
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