Effect of an inhibitor of DNA methylation on T cells. I. 5-Azacytidine induces T4 expression on T8+ T cells.

Maturing thymocytes express a series of cell surface glycoproteins which can be identified by monoclonal antibodies. The stage II or common thymocyte expresses the phenotype T4+T8+T6+T3-. In response to unknown signals, but presumably involving interactions with products of the major histocompatibility complex, the thymocyte suppresses either the T8 or T4 gene, becoming committed to the T4+T8- or T4-T8+ phenotype. With maturation, the thymocyte also becomes T6-T3+. To study whether DNA methylation may be involved in regulating expression of these determinants in mature T cells, we treated cloned interleukin 2-dependent T8- and T4-bearing T cells with 5-azacytidine (5-azaC), a nucleoside analog which inhibits methylation of newly synthesized DNA. In this report, we show that T8+ T cells treated with 5-azaC express the phenotype T8+T4+T6-T3+. Treatment of the same cells with hydroxyurea, an inhibitor of DNA synthesis, failed to induce T4 on T8+ cells. These results suggest that expression of the T4 gene may be suppressed by DNA methylation in mature T8+ cells.