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首页> 外文期刊>Transplant immunology >Impact of vaccine therapy using nuclear histone H1 on allograft survival in experimental organ transplantation.
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Impact of vaccine therapy using nuclear histone H1 on allograft survival in experimental organ transplantation.

机译:使用核组蛋白H1的疫苗治疗对实验器官移植中同种异体移植物存活的影响。

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BACKGROUND: We recently reported that autoreactive antibody (Ab) against nuclear histone H1 had been identified as an immunosuppressive factor in a rat tolerogenic orthotopic liver transplantation (OLT) model. The present study aimed to determine whether the up-regulation of antihistone H1 Ab by histone H1 vaccination leads to tolerance. METHODS: Histone H1-immunized rats were established by intraperitoneal vaccination with histone H1 at every two-weekly interval. By using mixed lymphocyte reaction (MLR) and heterotopic heart transplantation (HHT), the alloreactive T cell response and allograft survival of histone H1-immunized rats were compared with those of control rats. Cytokine and cellular profiles in histone H1-immunized rats were determined by reverse transcriptase polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and flow cytometry. RESULTS: Immunization with histone H1 in Freund's adjuvant induced alloreactive T cell unresponsiveness and prolonged heterotopic heart allograft survival. It also down-regulated the expression of major histocompatibility complex (MHC) class II and CD25 on splenic cells, elevated the T helper cell type 2 (Th2) skewing index (Interleukin (IL)-4/interferon (IFN)-gamma ratio or IL-4/IL-2 ratio) and modified the serum cytokine profiles. CONCLUSIONS: The present results suggest that histone H1 vaccination of transplant recipients, which leads to the production of immunosuppressive factor and the modification of the cytokine/cellular profiles, has great potential as a tolerance therapy for prospective transplantation.
机译:背景:我们最近报道,在大鼠耐受原位肝移植(OLT)模型中,针对核组蛋白H1的自身反应抗体(Ab)已被确定为免疫抑制因子。本研究旨在确定组蛋白H1疫苗对抗组蛋白H1 Ab的上调是否会导致耐受。方法:每两周一次腹腔内接种组蛋白H1,建立组蛋白H1免疫大鼠。通过混合淋巴细胞反应(MLR)和异位心脏移植(HHT),比较了组蛋白H1免疫大鼠的同种异体反应性T细胞反应和同种异体移植存活率。通过逆转录酶聚合酶链反应(RT-PCR),酶联免疫吸附测定(ELISA)和流式细胞仪确定组蛋白H1免疫大鼠的细胞因子和细胞谱。结果:在弗氏佐剂中用组蛋白H1免疫可诱导同种异体T细胞无反应性,并延长异位心脏同种异体移植的存活时间。它还下调了脾脏细胞上主要组织相容性复合物(MHC)II类和CD25的表达,提高了T型辅助细胞2型(Th2)的偏斜指数(白介素(IL)-4 /干扰素(IFN)-γ比或IL-4 / IL-2比值)并修改了血清细胞因子谱。结论:目前的结果表明,移植受者的组蛋白H1疫苗可导致免疫抑制因子的产生和细胞因子/细胞谱的改变,作为前瞻性移植的耐受疗法具有巨大潜力。

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