Anisomycin inhibits the behaviors of T cells and the allogeneic skin transplantation in mice.
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.
Xing
Feiyue
F
Department of Immunology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China. tfyxing@jnu.edu.cn
Yu
Zhe
Z
Liu
Jing
J
Di
Jingfang
J
Zeng
Shan
S
Chen
Di
D
Chen
Ling
L
Fang
Zhiyuan
Z
Guo
Zhongfeng
Z
Pan
Shan
S
Wang
Jiongkun
J
Li
Yuting
Y
Hao
Wenting
W
Fan
Zhenhua
Z
Teng
Zhenping
Z
Chen
Guoliang
G
Chen
Zhencheng
Z
Mao
Chengquan
C
Long
Yutian
Y
Liu
Na
N
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
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