title: Rapid histone deacetylation and transient HDAC association in the IL-2 promoter region of TSST-1-stimulated T cells.
abstract: It remains unclear how superantigen induces unresponsiveness in stimulated T cells. We analyzed the chromatin status of the interleukin-2 (IL-2) promoter region in T cells stimulated with toxic shock syndrome toxin-1 (TSST-1) superantigen using T cell receptor-transgenic T cells responding to ovalbumin (OVA) and TSST-1. Compared to OVA stimulation, naïve T cells cultured with TSST-1 showed lower IL-2 expression after transient enhancement. Coincidentally, the acetylated histone H3 (AcH3) level at the IL-2 promoter region was first enhanced, and then decreased, in TSST-1-stimulated T cells. At the reduction stage of AcH3, histone deacetylase-1 (HDAC1) was markedly associated with the IL-2 promoter region in a TSST-1-specific manner without HDAC1 over-expression. The enhancement of HDAC1 association and IL-2 suppression was prevented by pre-treatment with HDAC inhibitor, but not once the anergy status was established. These results suggest that recruitment of HDAC1 in the IL-2 promoter region at the early stimulation stage with TSST-1 plays a pivotal role in sAg-induced anergy.
authors.affiliation: Department of Immunology, Tokai University School of Medicine, Isehara-shi, Kanagawa 259-1193, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kametani
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Kanta
authors.initials: K
authors.lastname: Koduka
authors.forename: Takehito
authors.initials: T
authors.lastname: Sato
authors.forename: Ikumi
authors.initials: I
authors.lastname: Katano
authors.forename: Sonoko
authors.initials: S
authors.lastname: Habu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D017635:Clonal Anergy / Q000187:drug effects; D004768:Enterotoxins / Q000008:administration & dosage*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000276:immunology / Q000378:metabolism*; D006657:Histones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018089:Superantigens / Q000008:administration & dosage*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D006657:Histones; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D010047:Ovalbumin; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases