Triptolide promotes generation of FoxP3+ T regulatory cells in rats.
BACKGROUND
Triptolide (TPT), a component of the Chinese herb Triptergium wilfordii, has potent immunosuppressive and anti-inflammatory activity and is used clinically in recipients of kidney transplantation.


OBJECTIVE
This work aimed to investigate the effect of TPT on the differentiation of regulatory T lymphocytes (Tregs) from CD4+ cells in rats.


METHODS
MACS-purified rat CD4+ cells were costimulated with anti-CD3 and anti-CD28 in the presence of TGF-beta to induce the expression of FoxP3, which was detected by flow cytometry. TPT and cyclosporine A (CsA) were separately added into the cultures to observe the effect on the expression of FoxP3. Kidney transplantation was performed in rats that either received no treatment or were treated with TPT after transplantation.


RESULTS
TPT treatment enhanced the expression of FoxP3 in CD4+ cells, whereas CsA inhibited the FoxP3 expression. In the rat kidney transplantation model, the recipient rats treated with TPT survived longer than the control rats (18-19.83 vs 6.83 days, P<0.05). Meanwhile, the FoxP3+ T cells in the spleens of treated rats were higher than those from the untreated rats (12.4% vs 4.7%, P<0.05).


CONCLUSIONS
These data suggest that TPT may promote the differentiation of CD4+ cells to FoxP3+ Tregs. This would be at least one of the pathways responsible for the immunosuppressive activity of TPT.
Zhang
Gutian
G
Department of Urology, Nanjing Drum Tower Hospital, Nanjing University Medical School, 321 Zhong Shan Road, Nanjing 210008, China. zgr03summer@126.com
Liu
Yong
Y
Guo
Hongqian
H
Sun
Zeyu
Z
Zhou
Yi-Hua
YH
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
D015704:CD4 Antigens; D004224:Diterpenes; D004852:Epoxy Compounds; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C001899:triptolide