Rapamycin and tacrolimus differentially modulate acute graft-versus-host disease in rats after liver transplantation.
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 + or - 8.1 days) than those in the FK506 group (62.3 + or - 13.4 days) or the control group (22.9 + or - 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% + or - 0.8%) than in the FK506 group (1.7% + or - 0.4%) or the control group (2.0% + or - 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.
Xu
Guodong
G
Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multiorgan Transplantation (Ministry of Public Health), First Affiliated Hospital, Hangzhou, People's Republic of China.
Wang
Linyan
L
Chen
Wei
W
Xue
Fei
F
Bai
Xueli
X
Liang
Liang
L
Shen
Xuning
X
Zhang
Mangli
M
Xia
Dajing
D
Liang
Tingbo
T
D000818:Animals; D001706:Biopsy; D015704:CD4 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006706:Homeostasis; D007107:Immune System / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D020123:Sirolimus; D016559:Tacrolimus