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Prolonged survival of actively enhanced rat renal allografts despite accelerated cellular infiltration and rapid induction of both class I and class II MHC antigens

机译:尽管加速了细胞浸润并快速诱导了I类和II类MHC抗原,但积极增强的大鼠肾同种异体移植物的存活时间延长

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摘要

Administration of 1 ml of donor whole blood 7 d before renal transplantation produces long-term (greater than 100 d) graft survival in the DA (RT1a) into PVG (RT1c) rat strain combination. Using this model, the pattern and phenotype of infiltrating leukocytes were examined in rejecting and enhanced renal allografts, at days 1, 3, 5, and 7 after transplantation, by immunohistologic techniques. Paradoxically, enhanced grafts showed a more rapid and substantial leukocyte infiltrate, the phenotype of which was similar to that in rejecting grafts except for a reduced number of MRC OX-8+ cells and MRC OX-39+ cells. Graft infiltrating cells and splenocytes from transfused animals showed similar, although modest, levels of both nonspecific cytotoxicity and alloantigen-specific cytotoxicity. Immunohistologic analysis of MHC antigen distribution within the allograft revealed, unexpectedly, that enhanced grafts underwent an accelerated and extensive induction of both donor class I and class II MHC antigens. These findings were confirmed by allospecific quantitative absorption analysis, which showed severalfold increases in class I and class II MHC antigens by day 3 in enhanced grafts but not until day 5 in rejecting grafts. An additional observation was the more rapid disappearance of donor interstitial cells from enhanced grafts. These findings emphasize the overwhelming suppressive effect induced by an organ allograft after preoperative blood transfusion despite the associated induction of large numbers of potential effector cells and increased target antigen density within the graft.
机译:肾移植前7天施用1 ml供体全血可在DA(RT1a)和PVG(RT1c)大鼠品系组合中产生长期(大于100 d)移植物存活。使用该模型,在移植后第1、3、5和7天,通过免疫组织学技术检查了排斥和增强的肾脏同种异体移植物中浸润白细胞的模式和表型。矛盾的是,增强的移植物显示出更快和更大量的白细胞浸润,其表型与排斥移植物的表型相似,只是减少了MRC OX-8 +细胞和MRC OX-39 +细胞的数量。来自输血动物的移植物浸润细胞和脾细胞的非特异性细胞毒性和同种异体抗原特异性细胞毒性水平相似,尽管程度适中。对同种异体移植物中MHC抗原分布的免疫组织学分析出乎意料地表明,增强的移植物经历了供体I类和II类MHC抗原的加速和广泛诱导。这些发现被同种异体定量吸收分析所证实,该分析表明,增强型移植物中的I类和II类MHC抗原在第3天时增加了几倍,而排斥移植物中的第5天才出现。另一个观察结果是增强的移植物中供体间质细胞消失得更快。这些发现强调了术前输血后器官同种异体移植所产生的压倒性抑制作用,尽管伴随着大量潜在效应细胞的诱导和移植物中靶抗原密度的增加。

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