PReS-FINAL-1011: Can repeated T cell receptor stimulation lead to epigenetic reprogramming of the treg-specific demethylated region in human conventional T cells?

Abstract

Regulatory T (Treg) cells, vital to prevent autoimmune disease, can be identified by their expression of the forkhead box P3 (FoxP3) transcription factor. Human conventional T (Tconv) cells stimulated via the T cell receptor (TCR) can also express FoxP3. Although this can confer some intrinsic regulatory effects, controversy exists over whether FoxP3 expression alone gives rise to the Treg cell phenotype. Treg-specific demethylated region (TSDR) demethylation is thought to be a reliable marker of commitment to the Treg cell lineage. In most human studies, analysis of TSDR methylation status has been performed on bulk populations, where only a subpopulation of cells express FoxP3. However, TSDR demethylation may occur selectively in cells expressing the highest levels of FoxP3 protein. Previously, investigation of epigenetic modifications in FoxP3+ human Tconv cells has been hampered by the inability to separate cells on the basis of FoxP3 expression. Recently, however, a protocol has been published detailing a method for DNA extraction from cells that have been fixed and stained for FoxP3, permitting more informative phenotyping of TSDR methylation status.