Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells

doi:10.1016/j.intimp.2005.06.010

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	Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells
	Tang, W; Yang, Y; Zhang, F ; Li, YC ; Zhou, R ; Wang, JX ; Zhu, YN ; Li, XY ; Yang, YF ; Zuo, HP
刊名	INTERNATIONAL IMMUNOPHARMACOLOGY
	2005-12
卷号	5 期号:13-14 页码:1904-1913
关键词	(5R)-5-hydroxytriptolide graft-versus-host disease regulatory T cells immunosuppression
ISSN号	1567-5769
DOI	10.1016/j.intimp.2005.06.010
文献子类	Article
英文摘要	(5R)-5-hydroxytriptolide (LLDT-8) is a new compound derived from triptolide, which is the major immunosuppressive fraction of Tripterygium wilfordii Hook. F (TWHF). In this study, we demonstrated that administration of LLDT-8 (1 mg/kg/ day, p.o.) effectively prevented weight loss and death induced by allo-BMT (BLAB/c, H-2(d) to C57BL/6, H-2(b)),and extended survival in allo-BMT model of aGVHD. Following days 7 to 28 after allo-BMT, the allogeneic graft survived by increasing the number of engrafted cells (H-2(d)) in spleens of recipient mice with LLDT-8 treatment. To construe the immunosuppressive effects of LLDT-8, the splenocytes (H-2(d)) of LLDT-8 treated recipients (H-2(b)) were tested for the proliferative responses to donor antigen (H-2(d)), host antigen (H-2(b)) and mitogen (ConA) stimulations, respectively, the results indicated that LLDT-8 induced the T cells' unresponsiveness to donor and host antigens, while still maintaining response to ConA; Compared with the vehicle group of GVHD mice, administration of LLDT-8 significantly inhibited T cells to produce IFN-gamma with or without host antigen or ConA stimulation. Further studies indicated LLDT-8 had a normalizing effect on the ratio of CD4(+)/CD8(+) T cells, and increased CD4(+)CD25(+) T regulatory cells with the Foxp3 expression in splenocytes from LLDT-8 treated mice. The results outline the great potential of LLDT-8 as a therapeutic tool to induce suppression in GVHD. (c) 2005 Published by Elsevier B.V.
WOS关键词	BONE-MARROW TRANSPLANTATION ; WILFORDII HOOK F ; IMMUNOLOGICAL SELF-TOLERANCE ; TRIPTERYGIUM-WILFORDII ; IN-VITRO ; TRIPTOLIDE ; FOXP3 ; CD25(+) ; GVHD ; TRANSCRIPTION
WOS研究方向	Immunology ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000233686600013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273763]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Zuo, HP
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Grad Sch,Lab Immunopharmac, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Grad Sch,Lab Chem, Shanghai 201203, Peoples R China 3.Shanghai Univ TCM, Lab Immunol & Virol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Tang, W,Yang, Y,Zhang, F,et al. Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2005,5(13-14):1904-1913.
APA	Tang, W.,Yang, Y.,Zhang, F.,Li, YC.,Zhou, R.,...&Zuo, HP.(2005).Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells.INTERNATIONAL IMMUNOPHARMACOLOGY,5(13-14),1904-1913.
MLA	Tang, W,et al."Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells".INTERNATIONAL IMMUNOPHARMACOLOGY 5.13-14(2005):1904-1913.