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Rapamycin combined with allogenic immature dendritic cells selectively expands CD4+CD25+Foxp3+ regulatory T cells in rats.
Hepatobiliary Pancreat Dis Int. 2012 Apr; 11(2):203-8.HP

Abstract

BACKGROUND

Dendritic cells (DCs) can initiate the expansion of regulatory T cells (Tregs), which play an indispensable role in inducing transplantation tolerance. Some studies have investigated the effect of the immunosuppressant rapamycin (Rapa) on Tregs in vitro. However, the in vivo effect of Rapa combined with immature DCs (iDCs) on Tregs is unknown. This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectively expand the CD4+CD25+Foxp3+ Tregs in a rat model.

METHODS

Brown Norway rats were injected intravenously with 2X10(6) Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days. On day 8, the levels of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry. IL-2, IL-4, TGF-beta1, and IFN-gamma levels in serum were assessed by ELISA. The experimental animals were divided into four groups: control, Rapa-treated, iDC-treated, and combination-treated.

RESULTS

CD4+CD25+Foxp3+ Tregs comprised 7%-8% of CD4+ T cells in control rats. Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen. However, the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone. The levels of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3- T cells in CD4+ T cells did not significantly change in the combined group. The TGF-beta1 level in serum from the combined group increased significantly compared with the other groups.

CONCLUSIONS

A significantly higher percentage of CD4+ CD25+ Foxp3+ Tregs was found in rats treated with allogenic iDCs and a short course of Rapa, along with an increase in the TGF-beta1 level in serum. This improved protocol may be a promising therapeutic strategy to increase Tregs, which are beneficial to the induction of peritransplant tolerance.

Authors+Show Affiliations

Liver Transplantation Center, Third Affiliated Hospital, Transplantation Research Institute, Sun Yat-Sen University, Organ Transplantation Research Center of Guangdong Province, Guangzhou 510630, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22484590

Citation

Wang, Guo-Ying, et al. "Rapamycin Combined With Allogenic Immature Dendritic Cells Selectively Expands CD4+CD25+Foxp3+ Regulatory T Cells in Rats." Hepatobiliary & Pancreatic Diseases International : HBPD INT, vol. 11, no. 2, 2012, pp. 203-8.
Wang GY, Zhang Q, Yang Y, et al. Rapamycin combined with allogenic immature dendritic cells selectively expands CD4+CD25+Foxp3+ regulatory T cells in rats. HBPD INT. 2012;11(2):203-8.
Wang, G. Y., Zhang, Q., Yang, Y., Chen, W. J., Liu, W., Jiang, N., & Chen, G. H. (2012). Rapamycin combined with allogenic immature dendritic cells selectively expands CD4+CD25+Foxp3+ regulatory T cells in rats. Hepatobiliary & Pancreatic Diseases International : HBPD INT, 11(2), 203-8.
Wang GY, et al. Rapamycin Combined With Allogenic Immature Dendritic Cells Selectively Expands CD4+CD25+Foxp3+ Regulatory T Cells in Rats. HBPD INT. 2012;11(2):203-8. PubMed PMID: 22484590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapamycin combined with allogenic immature dendritic cells selectively expands CD4+CD25+Foxp3+ regulatory T cells in rats. AU - Wang,Guo-Ying, AU - Zhang,Qi, AU - Yang,Yang, AU - Chen,Wen-Jie, AU - Liu,Wei, AU - Jiang,Nan, AU - Chen,Gui-Hua, PY - 2012/4/10/entrez PY - 2012/4/10/pubmed PY - 2012/10/24/medline SP - 203 EP - 8 JF - Hepatobiliary & pancreatic diseases international : HBPD INT JO - HBPD INT VL - 11 IS - 2 N2 - BACKGROUND: Dendritic cells (DCs) can initiate the expansion of regulatory T cells (Tregs), which play an indispensable role in inducing transplantation tolerance. Some studies have investigated the effect of the immunosuppressant rapamycin (Rapa) on Tregs in vitro. However, the in vivo effect of Rapa combined with immature DCs (iDCs) on Tregs is unknown. This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectively expand the CD4+CD25+Foxp3+ Tregs in a rat model. METHODS: Brown Norway rats were injected intravenously with 2X10(6) Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days. On day 8, the levels of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry. IL-2, IL-4, TGF-beta1, and IFN-gamma levels in serum were assessed by ELISA. The experimental animals were divided into four groups: control, Rapa-treated, iDC-treated, and combination-treated. RESULTS: CD4+CD25+Foxp3+ Tregs comprised 7%-8% of CD4+ T cells in control rats. Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen. However, the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone. The levels of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3- T cells in CD4+ T cells did not significantly change in the combined group. The TGF-beta1 level in serum from the combined group increased significantly compared with the other groups. CONCLUSIONS: A significantly higher percentage of CD4+ CD25+ Foxp3+ Tregs was found in rats treated with allogenic iDCs and a short course of Rapa, along with an increase in the TGF-beta1 level in serum. This improved protocol may be a promising therapeutic strategy to increase Tregs, which are beneficial to the induction of peritransplant tolerance. SN - 1499-3872 UR - https://www.unboundmedicine.com/medline/citation/22484590/Rapamycin_combined_with_allogenic_immature_dendritic_cells_selectively_expands_CD4+CD25+Foxp3+_regulatory_T_cells_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/1590 DB - PRIME DP - Unbound Medicine ER -