Patterns of immune responses evoked by allogeneic hepatocytes -: Evidence for independent co-dominant roles for CD4+ and CD8+ T-cell responses in acute rejection
Patterns of immune responses evoked by allogeneic hepatocytes -: Evidence for independent co-dominant roles for CD4+ and CD8+ T-cell responses in acute rejection
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DOI：
10.1097/00007890-199908270-00019
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发表时间：
1999-08-27
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
导论.这是第一个在一系列的报告，其特征的免疫反应所诱发的同种异体肝细胞使用功能模型的肝细胞移植在小鼠中，方法，“供体”肝细胞表达转基因人α-1-抗胰蛋白酶（kA 1AT-FVB/N，H2（B））移植到用抗-CD 4，抗-CD 8，或抗-CD 4和抗-CD 8单克隆抗体（mAb）的组合。肝细胞排斥被确定为循环：ELISA可检测的转基因产物（hA 1AT）的损失。此外，一些C57 BL/6小鼠经历FVB/N异位心脏同种异体移植物的移植并用抗-CD 4 mAb治疗。对人工受体进行供者反应性同种抗体和供者反应性迟发型超敏反应（DTH）检测。同种异体肝细胞在正常C57 BL/6小鼠体内的中位存活时间为10天（未处理），10天（抗CD 4 mAb），14天（抗CD 8 mAb），35天（抗CD 4和抗CD 8单抗），B6 MHC II类基因敲除小鼠肝细胞的MST为10天（未处理）和21天（抗CD 8 mAb），心脏同种异体移植物的MST为11天（未处理）和>100天（抗CD 4 mAb）。供体反应性DTH反应在未治疗和单克隆抗体治疗的受者中很容易检测到。在未治疗的宿主中几乎检测不到供体反应性同种抗体。这些研究表明，同种异体肝细胞具有高度免疫原性，并通过CD 4（+）和CD 8（+）T细胞刺激强烈的细胞介导的免疫应答，即使在用可引起心脏同种异体移植物接受的试剂处理时也是如此。事实上，CD 4（+）或CD 8（+）T细胞似乎独立地引起肝细胞同种异体移植物排斥。同种异体肝细胞引起强烈的供体反应性DTH反应，但对供体反应性抗体产生的刺激很差，这是同种异体移植受者的一种不寻常的免疫反应模式。
Introduction. This is the first in a series of reports that characterizes immune responses evoked by allogeneic hepatocytes using a functional model of hepatocyte transplantation in mice,Methods, "Donor" hepatocytes expressing the transgene human alpha-1-antitrypsin (kA1AT-FVB/N, H2(q)) were transplanted into C57BL/6 (H2(b)) or MHC II knockout (H2b) hosts treated with anti-CD4, anti-CD8, or a combination of anti-CD4 and anti-CD8 monoclonal antibodies (mAbs), Hepatocyte rejection was determined as a loss of circulating: ELISA-detectable transgene product (hA1AT), In addition, some C57BL/6 mice underwent transplantation with FVB/N heterotopic cardiac allografts and were treated with anti-CD4 mAb, Cardiac allograft rejection was determined by palpation. Craft recipients were tested for donor-reactive alloantibodies and donor-reactive delayed-type hypersensitivity (DTH) responses.Results. The median survival time (MST) of allogeneic hepatocytes in normal C57BL/6 mice was 10 days (no treatment), 10 days (anti-CD4 mAb), 14 days (anti-CD8 mAb), and 35 days (anti-CD4 and anti-CD8 mAbs), The MST of hepatocytes in B6 MHC class II knockout mice was 10 days (no treatment) and 21 days (anti-CD8 mAb), The MST of cardiac allografts was 11 days (no treatment) and >100 days (anti-CD4 mAb). Donor-reactive DTH responses were readily detected in both untreated and mAb-treated recipients. Donor-reactive alloantibody was barely detectable in untreated hosts.Conclusions. These studies demonstrate that allogeneic hepatocytes are highly immunogenic and stimulate strong cell-mediated immune responses by both CD4(+) and CD8(+) T cells, even when treated with agents that can cause acceptance of cardiac allografts, Indeed, CD4(+) or CD8(+) T cells seem to independently cause hepatocellular allograft rejection. Allogeneic hepatocytes evoked strong donor-reactive DTH responses but were poor stimuli for donor-reactive antibody production, This is an unusual pattern of immune reactivity in allograft recipients.