HUMAN PERIPHERAL BLOOD LYMPHOCYTE RECONSTITUTED SEVERE COMBINED IMMUNODEFICIENT (hu‐PBL‐SCID) MICE: A Model for Human Islet Allograft Rejection
HUMAN PERIPHERAL BLOOD LYMPHOCYTE RECONSTITUTED SEVERE COMBINED IMMUNODEFICIENT (hu‐PBL‐SCID) MICE: A Model for Human Islet Allograft Rejection
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人外周血淋巴细胞重建严重联合免疫缺陷 (hu-PBL-SCID) 小鼠：人胰岛同种异体移植排斥模型
DOI：
10.1097/00007890-199406150-00004
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发表时间：
1994
期刊：
影响因子：
6.2
通讯作者：
D. Scharp
中科院分区：
文献类型：
--
作者：
R. Shiroki;N. Poindexter;E. Woodle;M. Hussain;T. Mohanakumar;D. Scharp
严重联合免疫缺陷（SCID）小鼠是研究人类免疫过程的理想动物模型。我们报告了一种可重复的人PBL（hu-PBL-SCID）移植SCID小鼠的技术的发展。我们的结果表明，在初次注射淋巴细胞后2天给予抗CD 3抗体刺激的人淋巴细胞的加强注射将使嵌合体建立的效率提高到86.7%（13/15）。人IG、人CD 3+细胞和人DNA在hu-PBL-SCID小鼠循环中的聚合酶链反应扩增检测之间也有良好的相关性。关于SCID小鼠中人类淋巴细胞的免疫功能仍然存在问题。在这项研究中，我们分析了人T细胞在SCID小鼠排斥移植到肾包膜下的人胰岛同种异体移植物的能力。通过人C-肽水平评估的人胰岛同种异体移植物功能证实在hu-PBL-SCID中移植后21天内胰岛同种异体移植物失败。相比之下，移植到未重建的SCID小鼠中的人胰岛继续发挥功能超过60天。从hu-PBL-SCID小鼠排斥的胰岛中回收的人T细胞显示出对HLA I类匹配的胰岛的特异性细胞溶解活性，而从hu-PBL-SCID小鼠脾中回收的细胞显示出对胰岛的最小特异性细胞毒性。这些结果表明，移植物浸润淋巴细胞被hu-PBL-SCID内移植的胰岛激活，导致人胰岛同种异体移植物的最终排斥。因此，抗CD 3抗体致敏的人PBL的植入导致具有功能上有能力的人免疫系统的小鼠-人嵌合体，其能够排斥人胰岛同种异体移植物。
Severe combined immunodeficient (SCID) mice have become a promising tool for the development of models of human immunologic process. We report the development of a reproducible technique for engrafting SCID mice with human PBL (hu-PBL-SCID). Our results show that a booster injection of anti-CD3 antibody stimulated human lymphocytes given 2 days after the initial injection of lymphocytes will improve the efficiency of chimera establishment to 86.7% (13 out of 15). There was also good correlation among detection of human Ig, human CD3+ cells, and human DNA by polymerase chain reaction amplification in the circulation of hu-PBL-SCID mice. Questions remain concerning the immune function of the human lymphoid cells in the SCID mouse. In this study, we analyzed the ability of human T cells in SCID mice to reject human islet allografts transplanted under the kidney capsule. Human islet allograft function assessed by human C-peptide levels demonstrated failure of islet allografts within 21 days after transplantation in hu-PBL-SCID. In contrast, human islets grafted in unreconstituted SCID mice continued to function for greater than 60 days. Recovered human T cells from rejected islets of hu-PBL-SCID mice displayed specific cytolytic activity against HLA class I-matched islets, while the recovered cells from spleen of hu-PBL-SCID mice showed minimal specific cytotoxicity against islets. These results suggest that graft-infiltrating lymphocytes were activated by the engrafted islets within the hu-PBL-SCID, causing the eventual rejection of the human islet allograft. Thus, engraftment of the anti-CD3 antibody-primed human PBL results in a mouse-human chimera with a functionally competent human immune system that is capable of rejecting a human islet allograft.