SPONTANEOUS ACCEPTANCE OF LIVER ALLOGRAFTS IN THE RAT - ANALYSIS OF THE IMMUNE-RESPONSE

SPONTANEOUS ACCEPTANCE OF LIVER ALLOGRAFTS IN THE RAT - ANALYSIS OF THE IMMUNE-RESPONSE
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DOI:
10.1097/00007890-199401001-00002
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发表时间:
1994-01-01
期刊:
影响因子:
6.2
通讯作者:
DALLMAN, MJ
DALLMAN, MJ
中科院分区:
医学2区
文献类型:
--
作者:
FARGES, O;MORRIS, PJ;DALLMAN, MJ

文献摘要

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在动脉化大鼠肝移植模型中,移植后2-8天,在排斥(DA至Lew)和自发接受(Lew-DA)移植物中比较了肝功能障碍的生物学指标和移植物浸润细胞的表型和体外功能。在此期间,排斥和非排斥同种异体移植物的受体在体重和血浆转氨酶水平方面的损失相似。然而,胆汁淤积的标志物在排斥移植物的接受者中从第3天和第4天开始增加,但在非排斥移植物的接受者和同系移植物的接受者中保持低水平和相似。从第2天到第6天的表型,IL-2的反应性,和供体特异性的细胞毒性潜力的白细胞浸润排斥和非排斥同种异体移植物是相当的。在第7天和第8天,尽管两种组合中T细胞亚群的比例相同,但未排斥移植物中活化的CD 4(+)移植物浸润细胞减少。同样在这个时候,供体特异性细胞毒性细胞不再检测到在非排斥移植,而活性已达到高峰,在拒绝grafts.These结果表明,肝移植在两个LEW->DA(移植物未被拒绝)和DA->LEW(移植物拒绝)应变组合进行组织损伤,但损伤的类型不同的两个组合。具体而言,胆汁淤积仅在随后被排斥的移植物中观察到。移植物损伤的差异发生在非常早的时间点(移植后3或4天),此时移植物浸润的强度或表型、其IL-2反应性或其细胞毒性潜力在两种组合之间均无变化。因此,如通过这些参数评估的,缺乏免疫反应性似乎不是LEW->DA菌株组合中肝移植物自发接受的原因。
In a model of arterialized rat liver transplantation, the biological indicators of liver dysfunction and the phenotype and in vitro function of graft-infiltrating cells have been compared in rejected (DA-to-Lew) and spontaneously accepted (Lew-to-DA) grafts, 2-8 days after grafting. Recipients of rejected and nonrejected allografts had, during this time, similar loss in body weight and plasma levels of transaminase. The markers of cholestasis, however, increased from days 3 and 4 onward in the recipients of rejected grafts, but remained low and similar in the recipients of nonrejected allografts and those of syngeneic grafts. From days 2 to 6 the phenotype, IL-2 responsiveness, and donor-specific cytotoxic potential of the leukocytes infiltrating rejected and nonrejected allografts were comparable. On days 7 and 8, although the proportion of T cell subpopulations was identical in both combinations, activated CD4(+) graft-infiltrating cells were reduced in the nonrejected grafts. Also at this time, donor-specific cytotoxic cells were no longer detected in nonrejected grafts, whereas activity had reached a peak in the rejected grafts.These results suggest that liver grafts in both the LEW-->DA (grafts not rejected) and DA-->LEW (grafts rejected) strain combinations undergo tissue damage, but that the type of damage differs between the two combinations. Specifically, cholestasis was only observed in grafts that would subsequently be rejected. The difference in graft damage occurred at a very early time point (3 or 4 days after grafting), at which time neither the intensity nor phenotype of the graft infiltrate, its IL-2 responsiveness, or its cytotoxic potential varied between the two combinations. Thus, a lack of immune reactivity, as assessed by these parameters, does appear not to be responsible for spontaneous acceptance of liver transplants in the LEW-->DA strain combination.