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Rapamycin combined with donor immature dendritic cells promotes liver allograft survival in association with CD4(+) CD25(+) Foxp3(+) regulatory T cell expansion.
Hepatol Res 2012; 42(2):192-202HR

Abstract

AIM

To determine whether donor immature dendritic cells (imDCs) combined with a short postoperative course of rapamycin (Rapa) has the ability to expand the CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells and prolong liver allograft survival.

METHODS

Orthotopic liver transplantation (OLT) was performed from Lewis rats to Brown Norway recipients. Three days before transplantation, animals were injected intravenously with 2 × 10(6) donor bone marrow-derived imDCs. Recipient rats (the combined treated group) also received Rapa for 7 d after liver transplantation. Additional groups received either imDCs alone, Rapa alone, or saline alone. Every six recipients from each group were killed at 14 days, 28 days after OLT. The changes of CD4(+) CD25(+) Foxp3(+) Treg cells in peripheral blood and spleen, histological changes of liver grafts, and serum cytokine levels were investigated. The other six recipients were left in each group to observe the animal survival.

RESULTS

Donor imDCs followed by a short postoperative course of Rapa induced long-term allograft survival. The percentage of CD4(+) CD25(+) Foxp3(+) Treg cells in CD4(+) T cells in the combination treatment group were significantly higher compared with the acute rejection group. Moreover, within the CD4(+) CD25(+) T cell population the combination treatment recipients maintained a higher incidence of Foxp3(+) T cells compared with the other groups. Despite the lower serum levels of interleukin (IL)-2, IL-12, and interferon-γ in the combined treated group, the cytokine levels in the combined treated group at 7 days after OLT was nearly twice that at 3 days after OLT but decreased significantly compared with the other groups at 28 days after OLT. Serum IL-10 level in the combined treated group was higher than the other groups.

CONCLUSIONS

A single imDC infusion followed by a short postoperative course of Rapa prolongs liver allograft survival and enhances the expansion of Treg cells. This optimal protocol may be a promising administration protocol for the peritransplant tolerance induction.

Authors+Show Affiliations

Liver Transplantation Center, the Third Affiliated Hospital, Sun Yat-sen University Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, 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

Language

eng

PubMed ID

22103959

Citation

Wang, Guo-Ying, et al. "Rapamycin Combined With Donor Immature Dendritic Cells Promotes Liver Allograft Survival in Association With CD4(+) CD25(+) Foxp3(+) Regulatory T Cell Expansion." Hepatology Research : the Official Journal of the Japan Society of Hepatology, vol. 42, no. 2, 2012, pp. 192-202.
Wang GY, Yang Y, Li H, et al. Rapamycin combined with donor immature dendritic cells promotes liver allograft survival in association with CD4(+) CD25(+) Foxp3(+) regulatory T cell expansion. Hepatol Res. 2012;42(2):192-202.
Wang, G. Y., Yang, Y., Li, H., Zhang, J., Li, M. R., Zhang, Q., & Chen, G. H. (2012). Rapamycin combined with donor immature dendritic cells promotes liver allograft survival in association with CD4(+) CD25(+) Foxp3(+) regulatory T cell expansion. Hepatology Research : the Official Journal of the Japan Society of Hepatology, 42(2), pp. 192-202. doi:10.1111/j.1872-034X.2011.00909.x.
Wang GY, et al. Rapamycin Combined With Donor Immature Dendritic Cells Promotes Liver Allograft Survival in Association With CD4(+) CD25(+) Foxp3(+) Regulatory T Cell Expansion. Hepatol Res. 2012;42(2):192-202. PubMed PMID: 22103959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapamycin combined with donor immature dendritic cells promotes liver allograft survival in association with CD4(+) CD25(+) Foxp3(+) regulatory T cell expansion. AU - Wang,Guo-Ying, AU - Yang,Yang, AU - Li,Hua, AU - Zhang,Jian, AU - Li,Min-Ru, AU - Zhang,Qi, AU - Chen,Gui-Hua, Y1 - 2011/11/22/ PY - 2011/11/23/entrez PY - 2011/11/23/pubmed PY - 2011/11/23/medline SP - 192 EP - 202 JF - Hepatology research : the official journal of the Japan Society of Hepatology JO - Hepatol. Res. VL - 42 IS - 2 N2 - AIM: To determine whether donor immature dendritic cells (imDCs) combined with a short postoperative course of rapamycin (Rapa) has the ability to expand the CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells and prolong liver allograft survival. METHODS: Orthotopic liver transplantation (OLT) was performed from Lewis rats to Brown Norway recipients. Three days before transplantation, animals were injected intravenously with 2 × 10(6) donor bone marrow-derived imDCs. Recipient rats (the combined treated group) also received Rapa for 7 d after liver transplantation. Additional groups received either imDCs alone, Rapa alone, or saline alone. Every six recipients from each group were killed at 14 days, 28 days after OLT. The changes of CD4(+) CD25(+) Foxp3(+) Treg cells in peripheral blood and spleen, histological changes of liver grafts, and serum cytokine levels were investigated. The other six recipients were left in each group to observe the animal survival. RESULTS: Donor imDCs followed by a short postoperative course of Rapa induced long-term allograft survival. The percentage of CD4(+) CD25(+) Foxp3(+) Treg cells in CD4(+) T cells in the combination treatment group were significantly higher compared with the acute rejection group. Moreover, within the CD4(+) CD25(+) T cell population the combination treatment recipients maintained a higher incidence of Foxp3(+) T cells compared with the other groups. Despite the lower serum levels of interleukin (IL)-2, IL-12, and interferon-γ in the combined treated group, the cytokine levels in the combined treated group at 7 days after OLT was nearly twice that at 3 days after OLT but decreased significantly compared with the other groups at 28 days after OLT. Serum IL-10 level in the combined treated group was higher than the other groups. CONCLUSIONS: A single imDC infusion followed by a short postoperative course of Rapa prolongs liver allograft survival and enhances the expansion of Treg cells. This optimal protocol may be a promising administration protocol for the peritransplant tolerance induction. SN - 1872-034X UR - https://www.unboundmedicine.com/medline/citation/22103959/Rapamycin_combined_with_donor_immature_dendritic_cells_promotes_liver_allograft_survival_in_association_with_CD4_+__CD25_+__Foxp3_+__regulatory_T_cell_expansion_ L2 - https://doi.org/10.1111/j.1872-034X.2011.00909.x DB - PRIME DP - Unbound Medicine ER -