The human immune system in hu-PBL-SCID mice.
The human immune system in hu-PBL-SCID mice.
复制标题
hu-PBL-SCID 小鼠的人体免疫系统。
DOI：
10.1016/0167-5699(95)80046-8
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Lehmann,PV
中科院分区：
文献类型：
--
作者：
Tary-Lehmann,M;Saxon,A;Lehmann,PV
严重联合免疫缺陷（SClD）小鼠可以稳定地移植人外周血淋巴细胞，产生hu-PBL-SCID嵌合体;本质上，这些小鼠具有人类免疫系统。在这里，Magdalena Tary-Lehmann，Andrew Saxon和Paul Lehmann讨论了这些嵌合体的免疫生物学。作者提出，hu-PBLSCID嵌合体的演变分为两个阶段。在移植后的前三周内，许多注射的细胞存活，人体免疫系统发挥作用。随后，选择抗小鼠反应性克隆，免疫系统变得无功能。这种情况下利用的BU-PBL-SCID模型的影响进行了讨论。在人体免疫系统的体内实验，例如在研究人类免疫缺陷病毒（HIV）感染，疫苗开发和药物测试，是技术和伦理上的困难。因此，具有人类免疫系统的小鼠对于生物医学研究将是极其有价值的。最近，已经引入了两种动物模型，可能会使这个梦想成为现实：hu-PBL-SCID嵌合体，通过将人外周血淋巴细胞（PBL）移植到严重联合免疫缺陷（SCID）小鼠中产生;和SCID-hu嵌合体，从胎儿组织移植物中获得其人类免疫系统。hu-PBL-SCID嵌合体的实验优势特征使其在生物医学研究的许多领域特别受欢迎。然而，对小鼠体内人类免疫系统的迷恋，以及急于利用它的想法，已经与定义嵌合体本质的努力背道而驰。从hu-PBL-SCID小鼠获得的任何数据的解释严重依赖的基本问题在很大程度上被忽视了：在小鼠中建立自身的人类免疫系统的生物学是什么？
Severe combined immunodeficiency (SClD) mice can be stably grafted with human peripheral blood lymphocytes, creating hu-PBL-SCID chimeras; essentially, these are mice with a human immune system. Here, Magdalena Tary-Lehmann, Andrew Saxon and Paul Lehmann discuss the immunobiology of these chimeras. The authors propose that hu-PBLSCID chimerism evolves in two phases. During the first three weeks after grafting, many of the injected cells survive and the human immune system is functional. Subsequently, anti-mouse-reactive clones are selected and the immune system becomes nonfunctional. The implications of this scenario for the utilization of the bu-PBL-SCID model are discussed.In viva experimentation on the human immune system, for instance in studies of human immunodeficiency virus (HIV) infections, vaccine development and drug testing, is technically and ethically difficult. Thus, mice that have a human immune system would be extremely valuable for biomedical research. Recently, two animal models have been introduced that might make this dream a reality: hu-PBL-SCID chimeras, generated by grafting human peripheral blood lymphocytes (PBLs) into severe combined immunodeficiency(SCID) mice’; and SCID-hu chimeras, which derive their human immune system from fetal tissue grafts?. The experimentally advantageous features of the hu-PBL-SCID chimeras have made them particularly popular in many areas of biomedical research. However, the fascination with the idea of a human immune system in a mouse, and the rush to exploit it, have detracted from the effort to define the very nature of the chimerism. The basic question, on which the interpretation of any data derived from hu-PBL-SCID mice heavily depends, has been largely neglected: what is the biology of the human immune system that establishes itself in the mouse?