Memory and flexibility of cytokine gene expression as separable properties of human TH1 and TH2 lymphocytes

CD4+ T cell priming under T helper type I (TH1) or TH2 conditions gives rise to polarized cytokine gene expression. We found that in these conditions human naive T cells acquired stable histone hyperacetylation at either the Ifng or Il4 promoter. Effector memory T cells showed polarized cytokine gene acetylation patterns in vivo, whereas central memory T cells had hypoacetylated cytokine genes but acquired polarized acetylation and expression after appropriate stimulation. However, hypoacetylation of the nonexpressed cytokine gene did not lead to irreversible silencing because most TH1 and TH2 cells acetylated and expressed the alternative gene when stimulated under opposite TH conditions. Such cytokine flexibility was absent in a subset of TH2 cells that failed to up-regulate T-bet and to express interferon-γ when stimulated under TH1 conditions. Thus, most human CD4+ T cells retain both memory and flexibility of cytokine gene expression.