Ruiz P, Coffman T M, Howell D N, Straznickas J, Scroggs M W, Baldwin W M, Klotman P E, Sanfilippo F
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Transplantation. 1988 Jan;45(1):1-7. doi: 10.1097/00007890-198801000-00002.
The effects of preoperative donor-specific blood transfusion (DSBT) on the physiologic, morphologic, and immunologic aspects of allograft responsiveness were evaluated in a rat renal transplant model, using the ACI (RT1a) into PVG (RT1c) high-responder strain combination. Indefinite graft survival (mean greater than 63 days) could be induced by DSBT administration alone. In comparison, animals receiving autologous blood transfusion (ABT) all died within 7 days posttransplantation. As assessed by clearance of inulin and paraaminohippurate, renal allograft function in DSBT-pretreated recipients at 6 days was equivalent to that of isograft recipients, and in contrast to the significant reduction seen in ABT treated rats. Likewise, thromboxane B2 (TXB2) production by ex-vivo-perfused allografts from DSBT-treated recipients was comparable to that of isografts, and significantly lower than that of allografts from ABT-treated rats. A significant inverse correlation was found between renal TXB2 production and inulin clearance. Despite these substantial differences in renal function and eicosanoid metabolism, morphologic evaluation of renal allografts from DSBT-enhanced and ABT-rejecting recipients at comparable time points showed equivalent histologic manifestations of rejection. In addition, immunohistologic labeling of renal allograft sections and fluorescence-activated cell sorter analysis of cells eluted from allografts showed the same phenotype and pattern of infiltrating T cell subsets in both groups. Specific antidonor cytotoxic T lymphocyte precursor (pCTL) frequencies of cells eluted from kidney grafts were equivalent in DSBT and ABT-pretreated animals, and both groups expressed significantly higher (but equivalent) pCTL frequencies in the kidneys than spleens. Comparisons of the lysis of PVG.R1 (RT1.Aa on a PVG background) and ACI targets indicated that cytotoxic responses from effector cells freshly eluted from DSBT and ABT kidneys were primarily directed against allogeneic class I major histocompatibility complex (MHC) specificities, whereas several long term T cell lines generated from 6-day kidney transplants of both groups expressed a predominant W3/25+ (T helper) phenotype and cytotoxic activity against donor specificities other than RT1.Aa class I MHC. Specific antidonor proliferative T lymphocyte (pPTL) precursor frequencies of cells eluted from renal allografts were also equivalent for both DSBT- and ABT-treated recipients, and the range of pPTL frequencies for allograft cell eluates was similar to that in spleens, regardless of the source of the transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)
在大鼠肾移植模型中,采用ACI(RT1a)到PVG(RT1c)高反应性品系组合,评估术前供体特异性输血(DSBT)对同种异体移植反应的生理、形态和免疫方面的影响。单独给予DSBT可诱导移植肾长期存活(平均大于63天)。相比之下,接受自体输血(ABT)的动物在移植后7天内全部死亡。通过菊粉和对氨基马尿酸清除率评估,DSBT预处理受体在术后6天的肾移植功能与同基因移植受体相当,与ABT处理大鼠中观察到的显著降低形成对比。同样,DSBT处理受体的体外灌注同种异体移植肾产生的血栓素B2(TXB2)与同基因移植肾相当,且显著低于ABT处理大鼠的同种异体移植肾。发现肾TXB2产生与菊粉清除率之间存在显著负相关。尽管在肾功能和类花生酸代谢方面存在这些显著差异,但在可比时间点对DSBT增强组和ABT排斥组的肾移植进行形态学评估,显示排斥反应的组织学表现相当。此外,肾移植切片的免疫组织化学标记以及从移植肾洗脱细胞的荧光激活细胞分选分析显示,两组中浸润T细胞亚群的表型和模式相同。从肾移植洗脱的细胞中,DSBT和ABT预处理动物的特异性抗供体细胞毒性T淋巴细胞前体(pCTL)频率相当,且两组在肾脏中的pCTL频率均显著高于脾脏。对PVG.R1(PVG背景上的RT1.Aa)和ACI靶细胞的裂解比较表明,从DSBT和ABT处理的肾脏中新鲜洗脱的效应细胞的细胞毒性反应主要针对同种异体I类主要组织相容性复合体(MHC)特异性,而从两组6天肾移植产生的几个长期T细胞系表现出主要的W3/25 +(辅助性T细胞)表型以及针对RT1.Aa I类MHC以外供体特异性的细胞毒性活性。从肾移植洗脱的细胞中,DSBT和ABT处理受体的特异性抗供体增殖性T淋巴细胞(pPTL)前体频率也相当,且移植肾细胞洗脱物的pPTL频率范围与脾脏相似,与输血来源无关。(摘要截断于400字)