Rapamycin and tacrolimus differentially modulate acute graft‐versus‐host disease in rats after liver transplantation | Zendy

Xu Guodong | Zendy; Wang Linyan | Zendy; Chen Wei | Zendy; Xue Fei | Zendy; Bai Xueli | Zendy; Liang Liang | Zendy; Shen Xuning | Zendy; Zhang Mangli | Zendy; Xia Dajing | Zendy; Liang Tingbo | Zendy

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Rapamycin and tacrolimus differentially modulate acute graft‐versus‐host disease in rats after liver transplantation

Author(s) -

Xu Guodong,

Wang Linyan,

Chen Wei,

Xue Fei,

Bai Xueli,

Liang Liang,

Shen Xuning,

Zhang Mangli,

Xia Dajing,

Liang Tingbo

Publication year - 2010

Publication title -

liver transplantation

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.814

H-Index - 150

eISSN - 1527-6473

pISSN - 1527-6465

DOI - 10.1002/lt.22003

Subject(s) - foxp3 , medicine , tacrolimus , il 2 receptor , liver transplantation , peripheral blood mononuclear cell , flow cytometry , regulatory t cell , transplantation , sirolimus , immunology , gastroenterology , pharmacology , t cell , immune system , biology , in vitro , biochemistry

Acute graft‐versus‐host disease (aGVHD) is a serious complication of liver transplantation (LTx); it occurs in 1% to 2% of liver allograft recipients. The condition has a poor prognosis and poses major diagnostic and therapeutic challenges. A rat model of aGVHD after LTx has been developed, and a relative decrease in regulatory T (Treg) cells has been shown to be associated with this model. Interest has been expressed in the effects of different immunosuppressive agents on CD4+CD25+Foxp3+ Treg cell homeostasis. Rats with aGVHD after LTx were treated with tacrolimus (FK506), rapamycin (RAPA), or no immunosuppressive drug. Those that received RAPA survived longer (91.4 ± 8.1 days) than those in the FK506 group (62.3 ± 13.4 days) or the control group (22.9 ± 1.2 days). Flow cytometry analysis showed that Treg cells, as a percentage of peripheral blood mononuclear cells (PBMCs), were more abundant in the RAPA group (6.8% ± 0.8%) than in the FK506 group (1.7% ± 0.4%) or the control group (2.0% ± 0.4%). Immunohistochemistry demonstrated more Foxp3+ staining of intestinal cells in the RAPA group than in the FK506 group or the control group. In conclusion, the reduced mortality induced by RAPA in a rat model of aGVHD after LTx was associated with higher percentages of CD4+CD25+Foxp3+ Treg cells in PBMCs in blood and tissues than those occurring after the administration of FK506. Liver Transpl 16:357–363, 2010. © 2009 AASLD.

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