Okamoto M, Stepkowski S M, Wang M, Kahan B D
Department of Surgery, University of Texas Medical School, Houston 77030, USA.
Transplantation. 2000 Oct 15;70(7):1060-7. doi: 10.1097/00007890-200010150-00012.
We aimed to identify the polymorphic epitopes that mitigate graft-versus-host disease (GvHD) and host-versus-graft response (HvGR) toward rat small bowel allografts in rats.
We tailored class I major histocompatibility complex (MHC) allochimeric antigens encoding 10 al-helical (alpha(1h)l58-80-RT1.Aa) or 4 (alpha(1h)l/u62-69-RT1.Aa) polymorphic amino acids. In the GvHD model, ACI (RT1a) donors were pretreated (day -14) with an intrathymic injection of alpha(1h)l58-80-RT1.Aa, alpha(1h)l/u62-69-RT1.Aa, or RT1.Al protein, with or without simultaneous intravenous injection of anti-T-cell receptor R73 monoclonal antibodies. Wistar-Furth (WF; RT1u) donors were tested with a similar protocol. In the HvGR model, ACI recipients were treated with a protocol designed to induce transplantation tolerance toward WF heart allografts: a portal vein injection of alpha(1h)l/u62-69-RT1.Aa protein and cyclosporine (4 mg/kg, intramuscular; days 0-6).
GvHD was prevented in all (ACI x LEW) F1 recipients (RT1a/l) by pretreating ACI donors with R73 monoclonal antibody and recipient RT1.Al or alpha(1h)l58-80-RT1.Aa protein. Similarly, pretreatment of WF donors with RT1.Aa protein also prevented GvHD in (ACI x WF) F1 recipients. However, in a combined GvHD/HvGR model, ACI recipient perioperative treatment designed to prevent HvGR only modestly prolonged WF small bowel allograft survival (27.7+/-5.3 days compared to 17.4+/-4.6 days in the cyclosporine-alone group). In contrast, application of the two protocols significantly prolonged WF allograft survival (55.6+/-34.6 days), with two of seven recipients surviving more than 100 days.
Simultaneous inhibition of GvHD and HvGR significantly prolongs small bowel allograft survival.
我们旨在鉴定可减轻大鼠对大鼠小肠同种异体移植的移植物抗宿主病（GvHD）和宿主抗移植物反应（HvGR）的多态性表位。
我们定制了编码10个α-螺旋（α(1h)l58 - 80 - RT1.Aa）或4个（α(1h)l/u62 - 69 - RT1.Aa）多态性氨基酸的I类主要组织相容性复合体（MHC）同种嵌合抗原。在GvHD模型中，ACI（RT1a）供体在第 - 14天接受胸腺内注射α(1h)l58 - 80 - RT1.Aa、α(1h)l/u62 - 69 - RT1.Aa或RT1.Al蛋白预处理，同时或不同时静脉注射抗T细胞受体R73单克隆抗体。Wistar - Furth（WF；RT1u）供体采用类似方案进行测试。在HvGR模型中，ACI受体采用旨在诱导对WF心脏同种异体移植产生移植耐受的方案进行治疗：门静脉注射α(1h)l/u62 - 69 - RT1.Aa蛋白和环孢素（4 mg/kg，肌肉注射；第0 - 6天）。
通过用R73单克隆抗体以及受体RT1.Al或α(1h)l58 - 80 - RT1.Aa蛋白预处理ACI供体，所有（ACI×LEW）F1受体（RT1a/l）的GvHD均得到预防。同样，用RT1.Aa蛋白预处理WF供体也可预防（ACI×WF）F1受体的GvHD。然而，在联合GvHD/HvGR模型中，旨在预防HvGR的ACI受体围手术期治疗仅适度延长了WF小肠同种异体移植的存活时间（与单独使用环孢素组的17.4±4.6天相比，为27.7±5.3天）。相比之下，应用这两种方案可显著延长WF同种异体移植的存活时间（55.6±34.6天），7只受体中有2只存活超过100天。
同时抑制GvHD和HvGR可显著延长小肠同种异体移植的存活时间。
