title: Anisomycin inhibits the behaviors of T cells and the allogeneic skin transplantation in mice.
abstract: There is still a lack of a high potent and low toxic immunosuppressive drug. We accidentally found that a quite low dose of anisomycin was sufficient to block proliferation of T cells. In this study, carboxy-fluorescein diacetate-succinimidyl ester staining showed that over 10.0 ng/mL of anisomycin markedly inhibited the proliferation of T cells induced by ConA. Propidium iodide staining revealed that anisomycin led to G0/G1 arrest and blocked S phase entry stimulated by ConA or phorbol 12, 13-dibutyrate plus ionomycin. Anisomycin down-regulated remarkably the CD69 and CD25 expression on the surface of T cells. The response of T cells was repressed by treatment of anisomycin, which was partly restored by adding exogenous interleukin-2, and there was no difference between anisomycin and dexamethasone, although the used dose of the latter was 100-fold of the former. The inhibition of cytotoxicity of T cells against 7919 cells by anisomycin was observed without the direct cytotoxicity to T cells or 7919 cells. The level of transforming growth factor-beta1 fell by <80.0 ng/mL in vitro and 30.0 mg/kg of anisomycin in vivo and enhanced by more than the doses. The treatment of anisomycin prolonged the survival of the transplanted skin and depressed the delayed type hypersensitivity development and the T-cell response in the skin-transplanted mice. Moreover, the effect of its restraining allograft rejection might be superior to cyclosporine A, with relatively slight toxic signs. These results indicate anisomycin significantly inhibits the behaviors of T cells and the transplantation rejection, providing important evidence for anisomycin as a novel immunosuppressant.
authors.affiliation: Department of Immunology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China. tfyxing@jnu.edu.cn
authors.forename: Feiyue
authors.initials: F
authors.lastname: Xing
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Jingfang
authors.initials: J
authors.lastname: Di
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Fang
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Guo
authors.forename: Shan
authors.initials: S
authors.lastname: Pan
authors.forename: Jiongkun
authors.initials: J
authors.lastname: Wang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Li
authors.forename: Wenting
authors.initials: W
authors.lastname: Hao
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Fan
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Teng
authors.forename: Guoliang
authors.initials: G
authors.lastname: Chen
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Chengquan
authors.initials: C
authors.lastname: Mao
authors.forename: Yutian
authors.initials: Y
authors.lastname: Long
authors.forename: Na
authors.initials: N
authors.lastname: Liu
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006084:Graft Rejection / Q000517:prevention & control; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous; D000099192:CD69 Antigens
chemical_list: D000841:Anisomycin; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D011500:Protein Synthesis Inhibitors; D000099192:CD69 Antigens