Characterization of immunosuppressive factors expressed in serum by rat tolerogenic liver transplantation
Characterization of immunosuppressive factors expressed in serum by rat tolerogenic liver transplantation
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DOI：
10.1016/j.transproceed.2004.12.290
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发表时间：
2005-01-01
影响因子：
0.9
通讯作者：
Chen, CL
中科院分区：
文献类型：
--
作者：
Nakano, T;Kawamoto, S;Chen, CL
背景在大鼠原位肝移植（奥尔特）耐受性模型中，奥尔特后受体血清（OLT后血清）具有较强的免疫抑制活性。本研究的目的是确定免疫抑制因子存在于早期OLT后血清。通过抑制混合淋巴细胞反应（MLR）在体外评价免疫抑制活性。通过蛋白质内部测序鉴定MLR抑制性IgG识别的自身抗原。OLT术后血清抑制MLR，OLT诱导的IgG是主要的免疫抑制因素。来自OLT后血清（2至3周）的IgG特异性地与脾细胞上的31、34和73-kd自身抗原反应。31-和34-kd抗原的内部序列与组蛋白H1分子的内部序列完全一致。免疫耗竭早期OLT后血清中的抗组蛋白H1抗体（Abs）消除了MLR抑制活性。此外，兔多克隆抗体定向组蛋白H1不仅显着抑制大鼠和人类MLR，但也延长心脏移植物的存活。流式细胞术分析显示，一些活PVG脾细胞染色与抗组蛋白H1抗体，这些阳性细胞增加刀豆蛋白A刺激。Western blot分析表明，在抗组蛋白H1抗体的膜组分中发现了几种交叉反应抗原。在这项研究中，我们提供的证据表明，自身反应抗体，对历史H1是一个主要的OLT诱导的移植物存活因素，并可能发挥至少在克服急性排斥反应阶段，建立固体同种异体移植物耐受的一部分。
Background. In a rat tolerogenic model of orthotopic liver transplantation (OLT), recipient serum after OLT (post-OLT serum) possesses strong immunosuppressive activity. This study aimed to identify immunosuppressive factors present in early post-OLT serum.Methods. Immunosuppressive activity was evaluated in vitro by inhibition of the mixed-lymphocyte reaction (MLR). Autoantigens recognized by MLR-inhibitory IgG were identified by the internal protein sequencing.Results. Recipient post-OLT serum inhibited MLR, and OLT-inducible IgG was the major immunosuppressive factor. IgG from post-OLT sera (2 to 3 weeks) specifically reacted to 31; 34; and 73-kd autoantigens on spleen cells. The internal sequences of the 31- and 34-kd antigens coincided completely with those of histone H1 molecules. Immunodepletion of anti-histone H1 antibodies (Abs) from early post-OLT serum abolished the MLR-inhibitory activity. Furthermore, rabbit polyclonal Ab-directed histone H1 not only significantly suppressed rat and human MLR but also prolonged survival of heart allografts. Flow-cytometric analysis revealed that some live PVG splenocytes were stained with antihistone H1 Abs, and that these positive cells increased on Con A stimulation. Western blot analysis indicated that several cross-reactive antigens against anti-histone H1 Abs were found in their membrane fraction.Conclusions. In this study we provide evidence that autoreactive Abs, against historic H1 are a major OLT-induced graft survival factor, and may play at least a part in overcoming the acute rejection phase to establish solid allograft tolerance.