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.
Liver Transpl. 2010 Mar;16(3):357-63. doi: 10.1002/lt.22003.
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.
急性移植物抗宿主病（aGVHD）是肝移植（LTx）的严重并发症；它发生在 1%至 2%的肝移植受者中。这种情况预后不良，对诊断和治疗构成重大挑战。已经建立了 LTx 后 aGVHD 的大鼠模型，并且已经表明调节性 T（Treg）细胞的相对减少与该模型有关。人们对不同免疫抑制剂对 CD4+CD25+Foxp3+Treg 细胞稳态的影响产生了兴趣。接受 LTx 后发生 aGVHD 的大鼠用他克莫司（FK506）、雷帕霉素（RAPA）或无免疫抑制剂治疗。接受 RAPA 的大鼠存活时间更长（91.4±8.1 天），而 FK506 组（62.3±13.4 天）或对照组（22.9±1.2 天）的大鼠存活时间更短。流式细胞术分析显示，RApa 组外周血单个核细胞（PBMCs）中 Treg 细胞的百分比（6.8%±0.8%）高于 FK506 组（1.7%±0.4%）或对照组（2.0%±0.4%）。免疫组织化学显示，RApa 组肠细胞中的 Foxp3+染色比 FK506 组或对照组更多。总之，在 LTx 后 aGVHD 大鼠模型中，RAPA 降低死亡率与 PBMCs 和组织中 CD4+CD25+Foxp3+Treg 细胞的百分比高于 FK506 治疗后相关。
