In vivo immunogenicity of purified allogeneic hepatocytes in a murine hepatocyte transplant model
In vivo immunogenicity of purified allogeneic hepatocytes in a murine hepatocyte transplant model
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DOI：
10.1097/00007890-199801150-00010
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发表时间：
1998-01-15
期刊：
影响因子：
6.2
通讯作者：
Orosz, CG
中科院分区：
文献类型：
--
作者：
Bumgardner, GL;Li, JS;Orosz, CG
背景。根据啮齿动物原位肝移植后自发耐受的高频率以及其他模型中门静脉耐受的现象，先前有报道称肝移植和肝细胞似乎具有耐受性。本研究的目的是表征移植到门静脉循环的异体肝细胞的体内免疫反应。方法：在肝细胞移植的功能模型中，将转人α 1-抗胰蛋白酶（hA1AT）的小鼠“供体”肝细胞通过脾内注射移植到宿主小鼠体内，测定宿主血清中分泌的hA1AT蛋白以测定移植物的存活，通过测定供体特异性同种异体抗体和延迟型超敏反应来评估宿主的免疫反应。在一些实验中，肝非实质细胞（NPCs）与同种异体肝细胞移植共移植。同种异体肝细胞移植到免疫能力强的宿主体内，在移植后7-10天导致宿主血清hA1AT的丧失，而同基因宿主维持了移植后肝细胞的长期存活，这反映在血清hA1AT的持续时间为100 - 20周。同种异体肝细胞移植导致供体特异性同种异体抗体和延迟型超敏反应的发展，以及第二次移植后加速肝细胞移植排斥反应的“第二组”反应，同种异体肝细胞移植时供体匹配的肝npc的预移植或共移植并不能延长肝细胞移植的存活时间。结论：同种异体肝细胞通过脾内注射进入门静脉循环是免疫原性的，而不是耐受原性的，在体内刺激弱的体液免疫反应和强的细胞介导的宿主免疫反应。同种异体肝细胞移植或预移植不能保护同种异体肝细胞免受免疫排斥。
Background. It has been reported previously that liver grafts and liver cells seem to be tolerogenic, based on the high frequency of spontaneous tolerance after orthotopic liver transplantation in rodents and on the phenomenon of portal venous tolerance in other models, The purpose of the current study was to characterize in vivo immune responses to allogeneic hepatocytes transplanted into the portal circulation.Methods, In this functional model of hepatocyte transplantation, "donor" hepatocytes from mice transgenic for human alpha 1-antitrypsin (hA1AT) were transplanted by intrasplenic injection into host mice and the secreted hA1AT protein measured in host serum to determine hepatocellular graft survival, Host immune responses were assessed by measurement of donor-specific alloantibodies and delayed-type hypersensitivity responses. In some experiments, liver nonparenchymal cells (NPCs) were co-transplanted with the allogeneic hepatocyte transplant.Results. Allogeneic hepatocyte transplant into immunocompetent hosts resulted in loss of host serum hA1AT by days 7-10 after transplant, whereas syngeneic hosts maintained long-term hepatocellular graft survival as reflected by persistence of serum hA1AT for >20 weeks. Allogeneic hepatocyte transplantation resulted in the development of donor-specific alloantibody and delayed-type hypersensitivity responses, as well as a "second set" response of accelerated hepatocellular graft rejection after a second transplant, Pretransplantation or co transplantation of donor-matched liver NPCs at the time of allogeneic hepatocyte transplantation did not prolong hepatocellular allograft survival.Conclusions, Allogeneic hepatocytes introduced into the portal circulation via intrasplenic injection are immunogenic not tolerogenic and stimulate a weak humoral and strong cell mediated host immune response in vivo. Go-transplantation or pretransplantation of allogeneic liver NPCs did not protect allogeneic hepatocytes from immunologic rejection.