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

✍ Scribed by Guodong Xu; Linyan Wang; Wei Chen; Fei Xue; Xueli Bai; Liang Liang; Xuning Shen; Mangli Zhang; Dajing Xia; Tingbo Liang

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 441 KB
• Volume: 16
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.22003

✦ Synopsis

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 CD4þCD25þFoxp3þ 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 6 8.1 days) than those in the FK506 group (62.3 6 13.4 days) or the control group (22.9 6 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% 6 0.8%) than in the FK506 group (1.7% 6 0.4%) or the control group (2.0% 6 0.4%). Immunohistochemistry demonstrated more Foxp3þ 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 CD4þCD25þFoxp3þ Treg cells in PBMCs in blood and tissues than those occurring after the administration of FK506.