CD8 expression is determined by DNA methylation.
A, CD4+ and CD8+ T cells from healthy humans and MRL/lpr mice were sorted for the assessment of DNA methylation. Murine DN T cells were sorted; human DN T cells were induced by TCR stimulation. In human (left) and murine (right) CD4+ T cells, the CD8 cluster was methylated. In CD8+ T cells from both species, the CD8 cluster was largely unmethylated. Stimulated human CD8+ T cells and murine DN T cells exhibited increased DNA methylation of the CD8 cluster. B, recruitment of the DNMT3a to the CD8 cluster was assessed using ChIP. In human and murine DN T cells, DNMT3a is recruited to the CD8 cluster. DNA methylation of the human CD8 cluster is more homogenous when compared with mice. In both species DNMT3a recruitment is particularly strong at CNS2, -6, -7, and -8.