5-Azacytidine induced inhibition of mitogenic response by agents that activate or augment activation of human peripheral blood T lymphocytes.

Previous work from our laboratory demonstrated the mitogenic response of human peripheral blood T lymphocytes by phytohemagglutinin (PHA), phorbol myristate acetate (PMA) and ionomycin, or interleukin 2 (IL-2). Increasing levels of incorporated 5-azacytosine inhibited the action of the methyltransferase suggesting that incorporation of 5-azacytosine into DNA could be responsible for the inhibiting effect of 5-azacytidine (5-aza-CR) on DNA methylation. In this study, we first demonstrated the inhibition of mitogenic response by agents, such as PHA, PMA and ionomycin, or IL-2, that activate or augment activation of human peripheral blood T cells by treatment of the analog 5-azacytidine. Over 1 microM of 5-azacytidine, we detected significant inhibition of proliferative response and over 5 microM of 5-azacytidine toxic effect of cell viability. We found no significant change of T cell subsets after treatment of 5-azacytidine.