Abstract
We investigated whether epigenetic modification agents can convert naïve T cells to regulatory T cells (T regs) which are responsible for limiting immune responses and maintaining self-tolerance. We treated splenic CD4 +/CD25 − naïve T cells from BALB/c mice with the DNA-methyltransferase inhibitor 5-aza-2′-deoxycytidine (5AzaD) or the histone protein deacetylase (HDAC) inhibitor Trichostatin A (TSA), and measured the effects on the expression of FOXP3, which encodes a transcription factor ( FOXP3) that regulates T reg development. FOXP3 expression in naïve T cells was increased by 5AzaD or TSA treatment, administered 72 hours after T-cell receptor (TCR) stimulation with anti-CD3 plus anti-CD28. The T regs induced by 5AzaD or TSA expressed greater amounts of the FOXP3 protein than the control and the natural T regs. The analysis of T reg-associated markers also showed T reg phenotypes (CD25 +/CTLA4 +/GITR +/CD127 −). Finally, the induced T reg population also displayed T-cell suppression. These data suggested that epigenetic modification agents can induce FOXP3 expression, promoting the conversion of naïve T cells to T regs.
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