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[肝移植后的免疫机制。大鼠实验研究]

[Immunologic mechanism following liver transplantation. An experimental study in the rat].

作者信息

Lie T S, Galkowska H, Jaeger K, Niehaus K J

出版信息

Langenbecks Arch Chir. 1983;360(1):17-27. doi: 10.1007/BF01255580.

DOI:10.1007/BF01255580
PMID:6348454
Abstract

To investigate the immunological status of hepatic grafts we transplanted livers from different inbred rats orthotopically on 58 LEW rats; rearterialization of the grafts was achieved with an hepatico aortal segment of the donor. Survival time depended on the donor strain; LBNF1-allografts survived in 67% (n = 12), WiS- in 60% (n = 20) and BUF- in 43% (n = 14) indefinitely. In the DA-to-LEW-combination we found no long-term survivor. Liver perfusates (LP) were prepared from 10 BDE and 10 LEW; after keeping the livers for 6 h at room temperature we perfused via portal vein with 2 ml/g Ringer's solution five times. The treatment of BDE-kidney recipients (LEW) with LP showed prolonged survival; at 5 days application 10.2 +/- 1.3 d (control: 6.5 +/- 0.5 d; P less than 0.001), at 10 days treatment 15.3 +/- 7.3 d. In vitro LP inhibited the PHA-stimulation of LEW lymphoid cells in more than 90% and the ConA-stimulation of LEW spleen cells in more than 95%. In MLC LP showed strong inhibitory effect (inhibition rate greater than 97%) even when different combinations of responding and stimulating cells were used. We assume that an unspecific immunosuppressive hepatic factor is released from ischemic damaged liver grafts which is able to prevent rejection in the induction phase. In WiS-liver recipients surviving for more than 4 months GvHR was tested after splenectomy with spleen cells. All tests showed a grade III reaction. Donor-specific skin grafts which were transplanted on these recipients survived indefinitely while third party skin grafts were regularly rejected (7.6 +/- 0.5 d). We therefore can conclude that the cellular immunosurveillance is intact, but the immunological response against donor-specific antigens is reduced. With transfer of serum from long-term-surviving WiS-liver recipients (greater than 6 months) WiS-kidney grafted LEW were able to survive also prolonged (20.7 +/- 3.4 d, control 6.2 +/- 1.0 d; P less than 0.001). Lymphoid cell transfer (1 X 10(8)) did did not result in significant prolongation of survival time (8.0 +/- 2.0 d). These observations suggest that in the steady phase specific humoral transfer factors are responsible for prolonged survival of hepatic grafts.

摘要

为研究肝移植的免疫状态,我们将不同近交系大鼠的肝脏原位移植到58只LEW大鼠上;通过供体的肝主动脉段实现移植肝的再动脉化。存活时间取决于供体品系;LBNF1同种异体移植物的长期存活率为67%(n = 12),WiS为60%(n = 20),BUF为43%(n = 14)。在DA对LEW的组合中,我们未发现长期存活者。从10只BDE和10只LEW大鼠制备肝灌注液(LP);将肝脏在室温下保存6小时后,经门静脉用2 ml/g林格氏液灌注5次。用LP处理BDE肾移植受体(LEW)可延长存活时间;在应用5天时为10.2±1.3天(对照组:6.5±0.5天;P<0.001),在应用10天时为15.3±7.3天。体外LP抑制LEW淋巴细胞对PHA的刺激超过90%,抑制LEW脾细胞对ConA的刺激超过95%。在混合淋巴细胞培养中,即使使用不同组合的反应细胞和刺激细胞,LP也显示出强烈的抑制作用(抑制率>97%)。我们推测,缺血损伤的肝移植物释放出一种非特异性免疫抑制肝因子,它能够在诱导期预防排斥反应。在存活超过4个月的WiS肝移植受体中,脾切除后用脾细胞检测移植物抗宿主反应(GvHR)。所有检测均显示为III级反应。移植到这些受体上的供体特异性皮肤移植物长期存活,而第三方皮肤移植物则被定期排斥(7.6±0.5天)。因此,我们可以得出结论,细胞免疫监视功能完好,但针对供体特异性抗原的免疫反应降低。将长期存活(>6个月)的WiS肝移植受体的血清转移后,移植了WiS肾的LEW大鼠也能延长存活时间(20.7±3.4天,对照组6.2±1.0天;P<0.001)。淋巴细胞转移(1×10⁸)并未导致存活时间显著延长(8.0±2.0天)。这些观察结果表明,在稳定期,特异性体液转移因子是肝移植物长期存活的原因。

相似文献

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[Immunologic mechanism following liver transplantation. An experimental study in the rat].[肝移植后的免疫机制。大鼠实验研究]
Langenbecks Arch Chir. 1983;360(1):17-27. doi: 10.1007/BF01255580.
2
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Chir Forum Exp Klin Forsch. 1980:121-4.
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Rejection of spontaneously accepted rat liver allografts with recipientinterleukin-2 treatment or donor irradiation.通过受体白细胞介素-2治疗或供体照射来排斥自发接受的大鼠肝脏同种异体移植物。
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The persistence of regulatory cells developing after rat spontaneous liver acceptance.大鼠自发性肝移植后发育的调节性细胞的持续性。
Surgery. 2005 Aug;138(2):329-34. doi: 10.1016/j.surg.2005.06.001.

引用本文的文献

1
[Immunologic tolerance after experimental liver transplantation].[实验性肝移植后的免疫耐受]
Langenbecks Arch Chir. 1995;380(5):281-7. doi: 10.1007/BF00184103.

本文引用的文献

1
INVASION AND DESTRUCTION OF HOMOLOGOUS KIDNEY BY LOCALLY INOCULATED LYMPHOID CELLS.局部接种的淋巴细胞对同种肾的侵袭与破坏
J Exp Med. 1964 Sep 1;120(3):329-48. doi: 10.1084/jem.120.3.329.
2
Anomalous relationship between duration of ischemia and survival after orthotopic transplantation of the liver.肝脏原位移植后缺血持续时间与生存率之间的异常关系。
Transplantation. 1981 Mar;31(3):228.
3
Graft adaptation: studies on possible mechanisms in long-term surviving rat renal allografts.移植物适应:长期存活大鼠肾同种异体移植可能机制的研究
Transplantation. 1980 Jul;30(1):73-80.
4
Fully allogeneic liver grafting in rats induces a state of systemic nonreactivity to donor transplantation antigens.大鼠全异体肝移植可诱导机体对供体移植抗原产生全身性无反应状态。
Transplantation. 1980 May;29(5):429-31. doi: 10.1097/00007890-198005000-00021.
5
Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test.同种移植的血清分型。18. 微滴淋巴细胞细胞毒性试验的改进。
Transplantation. 1968 Nov;6(8):913-27. doi: 10.1097/00007890-196811000-00006.
6
An improved technique of renal transplantation in the rat.大鼠肾移植的一种改良技术。
Surgery. 1967 May;61(5):771-3.
7
Observations of orthotopic liver transplantation in the pig.猪原位肝移植的观察
Br Med J. 1967 May 20;2(5550):478-80. doi: 10.1136/bmj.2.5550.478.
8
Passive enhancement of rat renal allografts with only partial cover of the incompatible Ag-B specificities.仅部分覆盖不相容的Ag-B特异性对大鼠肾同种异体移植进行被动增强。
Transplantation. 1974 Nov;18(5):436-42. doi: 10.1097/00007890-197411000-00008.
9
Passive enhancement of homozygous renal allografts in the rat.大鼠纯合子肾移植的被动增强作用
Transplantation. 1974 Nov;18(5):429-35. doi: 10.1097/00007890-197411000-00007.
10
[Liver transplantation (current status and perspectives)].[肝移植(现状与展望)]
Zentralbl Chir. 1973 Nov 16;98(46):1633-41.