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.
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Richardson
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Kahn
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Lovett
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Hudson
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000096:biosynthesis*; D001374:Azacitidine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002999:Clone Cells / Q000276:immunology; D004247:DNA / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008745:Methylation; D010641:Phenotype; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007166:Immunosuppressive Agents; D004247:DNA; D001374:Azacitidine