title: Induction of CD4+ regulatory T cells by 12-O-tetradecanoylphorbol 13-acetate in mice. Part 1: The strain difference in this induction.
abstract: 12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of signal transduction, induced antigen-nonspecific regulatory T (Tr) cells for delayed-type hypersensitivity (DTH) in the spleen. A marked strain difference in the induction of Tr cells was observed when the study was performed by using the several strains of mice at 6-8 weeks old. TPA painting induced CD4+Tr cells in C3H/He (H-2k), C3H/HeN (H-2k), DBA/2 (H-2d) and AKR/N (H-2k) mice, but not in C57BL/6 (H-2b), C57BL/10 (H-2b), BALB/c (H-2d) and A/J (H-2a). Regulatory cells were also induced by incubating spleen cells from unprimed mice with TPA in vitro and were seemed to act by the production of soluble factor(s). A downregulatory activity of the soluble factor(s) was abrogated by SXC-1 (anti-IL-10 monoclonal antibody), but not by SXC-2 (anti-IL-10 monoclonal antibody) and anti-IL-4. For purification of the factor(s), we established the T cell hybridoma 4C5-1 by the fusion of spleen cells from TPA-treated C3H/He mice with AKR thymoma Bw5147 cells. The 4C5-1 cells secrete the factor(s) which can inhibit DTH response. The inhibitory activity of the factor(s) could be neutralized by SXC-1, but not by SXC-2, anti-IL-4, anti-IL-6 and anti-TGF-beta antibodies. The factor(s) could not affect the proliferation and IFN-gamma production of alpha s1-casein-specific 3D20 Th1 cells. The factor(s) termed DIF (DTH Inhibitory Factor) may be a novel cytokine, since they have reduced the footpad swelling response by local injection, and have no immune crossreactivity with the DTH regulatory cytokines and no inhibitory activity for in vitro Th1 response.
authors.affiliation: Department of Medicinal Information, School of Pharmaceutical Sciences, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. tanego@pharm.showa-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Negoro
authors.forename: F
authors.initials: F
authors.lastname: Iinuma
authors.forename: T
authors.initials: T
authors.lastname: Tobe
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D000954:Antigens, Surface; D015704:CD4 Antigens / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D006825:Hybridomas / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000954:Antigens, Surface; D015704:CD4 Antigens; D007202:Indicators and Reagents; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate