Cutting edge: Stable epigenetic inheritance of regional IFN-gamma promoterdemethylation in CD44(high)CD8(+) T lymphocytes

Genomic DNA methylation patterns influence the development and maintenance of function during cellular differentiation. Methylation of regulatory sequ ences can have long-lasting effects on gene expression if inherited in an e pigenetic manner. Recent work suggests that DNA methylation has a regulator y role in differential cytokine gene expression in primary T lymphocytes, H ere we show, by clonal Lineage analysis, that methylation patterns in the I FN-gamma promoter exhibit long term faithful inheritance in CD44(high)CD8() T cells and their progeny, through 16 cell divisions and a clonal expansi on of 5 orders of magnitude. Moreover, the demethylated IFN-gamma promoter is faithfully inherited following the withdrawal of T cell stimulation and the loss of detectable IFN-gamma mRNA, consistent with passive rather than active maintenance mechanisms. This represents a form of stable cellular me mory, of defined epigenetic characteristics, that may contribute to the mai ntenance of T cell cytokine expression patterns and T cell memory.