Bowles M J, Wood R F, Pockley A G
Division of Clinical Sciences (NGH), Clinical Sciences Centre (University of Sheffield), Northern General Hospital, UK.
Transplantation. 2001 Jan 15;71(1):32-6. doi: 10.1097/00007890-200101150-00006.
Given the potential influence of alloantibodies on organ graft outcome, this study investigated the induction of antigraft and antirecipient antibodies after allogeneic and semiallogeneic rat small bowel transplantation.
Fully allogeneic, unidirectional rejection and unidirectional graft-versus-host disease (GvHD) heterotopic small bowel transplantation was performed using DA, PVG, and (PVGxDA)F1 donor-recipient combinations. Serum was obtained before and at time points after transplantation and incubated with blood from untransplanted DA and PVG rats. Antibody binding to T cells was detected by whole blood flow cytometry using FITC-conjugated anti-rat IgM murine monoclonal antibody. Antibody levels were determined by reference to a standard curve of fluorescent intensity generated using a serum sample with known anti-target cell IgM activity. Data are presented as arbitrary units/ml (AU/ml).
In the PVG-->DA combination, five of six DA recipients had detectable anti-graft (PVG) antibodies by day 4 after transplantation (mean 72 AU/ml) and all animals were positive by day 6 (976 AU/ml). Antirecipient (DA) antibodies were also induced, however, they were only apparent after 6 days in five of eight animals (90 AU/ml). Antigraft (DA) antibody responses were also induced in the DA-->PVG combination (day 6-218 AU/ml), however no antirecipient (PVG) response was apparent. Transplantation induced antirecipient (DA) antibodies in the unidirectional GvHD model (day 6-90 AU/ml) and an anti-graft (PVG) response in the unidirectional rejection model (day 6-60 AU/ml). However, the latter was quantitatively lower than that generated in the PVG-->DA combination (day 6-976 AU/ml).
Antigraft and antirecipient antibody responses are simultaneously induced after fully allogeneic small bowel transplantation, despite rejection being the predominant clinical feature. Further studies are required to elucidate their influence on graft outcome.
鉴于同种异体抗体对器官移植结果的潜在影响，本研究调查了同种异体和半同种异体大鼠小肠移植后抗移植物和抗受体抗体的诱导情况。
使用DA、PVG和（PVG×DA）F1供体 - 受体组合进行完全同种异体、单向排斥和单向移植物抗宿主病（GvHD）异位小肠移植。在移植前及移植后的各个时间点采集血清，并与未移植的DA和PVG大鼠的血液一起孵育。使用异硫氰酸荧光素（FITC）偶联的抗大鼠IgM鼠单克隆抗体，通过全血流式细胞术检测抗体与T细胞的结合情况。通过参考使用具有已知抗靶细胞IgM活性的血清样本生成的荧光强度标准曲线来确定抗体水平。数据以任意单位/毫升（AU/ml）表示。
在PVG→DA组合中，六只DA受体中有五只在移植后第4天可检测到抗移植物（PVG）抗体（平均72 AU/ml），到第6天所有动物均呈阳性（976 AU/ml）。抗受体（DA）抗体也被诱导产生，然而，仅在八只动物中的五只在6天后才明显出现（90 AU/ml）。在DA→PVG组合中也诱导了抗移植物（DA）抗体反应（第6天 - 218 AU/ml），然而未观察到明显的抗受体（PVG）反应。移植在单向GvHD模型中诱导了抗受体（DA）抗体（第6天 - 90 AU/ml），在单向排斥模型中诱导了抗移植物（PVG）反应（第6天 - 60 AU/ml）。然而，后者在数量上低于PVG→DA组合中产生的抗体（第6天 - 976 AU/ml）。
尽管排斥是主要的临床特征，但在完全同种异体小肠移植后同时诱导了抗移植物和抗受体抗体反应。需要进一步研究以阐明它们对移植结果的影响。
