Kinetics of intragraft cytokine expression, cellular infiltration, and cell death in rejection of renal allografts compared with acceptance of liver allografts in a rat model - Early activation and apoptosis is associated with liver graft acceptance
Kinetics of intragraft cytokine expression, cellular infiltration, and cell death in rejection of renal allografts compared with acceptance of liver allografts in a rat model - Early activation and apoptosis is associated with liver graft acceptance
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DOI：
10.1097/00007890-199805270-00015
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发表时间：
1998-05-27
期刊：
影响因子：
6.2
通讯作者：
Bishop, GA
中科院分区：
文献类型：
--
作者：
Sharland, A;Shastry, S;Bishop, GA
背景PVG-Dark Agglutination大鼠品系组合的肝移植是自发耐受的，而相同品系组合的肾移植在7-9天内被排斥。为了鉴定可能产生关于该菌株组合中耐受性诱导机制的进一步信息的器官特异性差异，在第1、3、5和7天收获肝或肾移植物、脾和引流淋巴结，并通过免疫组织化学、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定和干扰素-γ的逆转录酶-聚合酶链反应进行检查，IL-2、IL-4和IL-10。肾移植排斥反应与单核细胞浸润的进行性发展有关，淋巴细胞活化和细胞因子上调的标志物从第3天开始出现，在排斥反应的高峰期，在第5-7天观察到许多凋亡的实质细胞。相反，肝脏同种异体移植耐受性与活化T细胞的更快浸润和细胞因子表达的更早增加有关，但细胞浸润程度更有限。与早期活化同时，在白细胞浸润区域发现高水平的凋亡，与移植物中活化T细胞的消失平行。肝移植物中浸润性白细胞的凋亡可能是诱导自发性肝移植耐受的一个重要过程，也可能是在耐受性肝内观察到的效应子反应的流产性质的基础。相比之下，同种异体肾移植物中的活化细胞在相同菌株组合中存活和增殖，表达高水平的细胞因子，并且有效地导致移植物破坏。
Background Liver transplants in the rat strain combination PVG-to-Dark Agouti are spontaneously tolerated, whereas kidney transplants in the same strain combination are rejected in 7-9 days.Methods. To identify organ-specific differences that might yield further information about the mechanism of tolerance induction in this strain combination, liver or kidney grafts, spleen, and draining lymph nodes were harvested at days 1, 3, 5, and 7, and examined by immunohistochemistry, terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay, and reverse transcriptase-polymerase chain reaction for interferon-gamma, interleukin (IL)-2, IL-4, and IL-10.Results. Renal allograft rejection was associated with the progressive development of an intense mononuclear cell infiltrate, Markers of lymphocyte activation and cytokine up-regulation appeared from day 3, and many apoptotic parenchymal cells were noted on days 5-7, at the peak of rejection. conversely, liver allograft tolerance was associated with more rapid infiltration by activated T cells and earlier increases in cytokine expression, but with a more limited degree of cellular infiltration. Concurrent with the early activation, high levels of apoptosis were found in areas of leukocyte infiltrate, paralleling the disappearance of activated T cells from the graft between days 3 and 5.Conclusions. Apoptosis of infiltrating leukocytes in liver allografts may represent an important process in the induction of spontaneous liver transplant tolerance and may underlie the abortive nature of the effector response observed within tolerated livers. In contrast, activated cells in renal allografts in the same strain combination survive and proliferate, express high levels of cytokines, and are efficient in bringing about graft destruction.