TRANSFER OF A FUNCTIONAL HUMAN IMMUNE-SYSTEM TO MICE WITH SEVERE COMBINED IMMUNODEFICIENCY
TRANSFER OF A FUNCTIONAL HUMAN IMMUNE-SYSTEM TO MICE WITH SEVERE COMBINED IMMUNODEFICIENCY
复制标题
DOI：
10.1038/335256a0
复制
发表时间：
1988-09-15
期刊：
影响因子：
64.8
通讯作者：
WILSON, DB
中科院分区：
文献类型：
--
作者：
MOSIER, DE;GULIZIA, RJ;WILSON, DB
艾滋病研究迫切需要更好的实验系统，这使得现有动物模型的缺点以及人类免疫反应和病毒发病机制研究的实际和伦理局限性成为人们关注的焦点1,2。目前对人类免疫反应的研究仅限于相对严格的体内实验和几个体外系统，这些系统虽然有用，但仅允许短期研究并支持对少数抗原的反应2。这两种模型都不太适合研究免疫系统疾病的发病机制。我们在此报告，注射人外周血白细胞（PBL）可以使患有严重联合免疫缺陷（SCID）的小鼠长期稳定地重建功能性人类免疫系统4。移植到 SCID 小鼠体内的人 PBL 数量增加并存活至少六个月；重组小鼠表现出人免疫球蛋白的自发分泌，并且在用破伤风类毒素免疫后诱导特异性人抗体反应。 PBL 中存在的所有主要细胞群均存在于 SCID 受体的淋巴组织和血液中，尽管长期受体中 B 细胞、T 细胞亚群和单核细胞/巨噬细胞的相对比例与正常 PBL 中发现的不同，并且在移植了 50 x 106 或更多来自 Epstein-Barr 病毒 (EBV) 血清阳性供体的 PBL 的小鼠中，经常会出现 EBV 阳性 B 细胞淋巴瘤。我们的结果表明，将人类淋巴细胞异种移植到 SCID 小鼠中可能为研究正常人类免疫功能、免疫系统对病原体的反应以及淋巴瘤发生的早期事件提供有用的模型。
The pressing need for a better experimental system for AIDS research has brought into sharp focus the shortcomings of available animal models and the practical and ethical limitations of studies of immune responses and viral pathogenesis in humans1,2. Current studies of the human immune responses are limited to relatively restrictivein vivoexperiments and severalin vitrosystems that, although useful, allow only short-term studies and support responses to a few antigens2. Neither model is particularly amenable to studies of the pathogenesis of diseases of the immune system. We report here that injection of human peripheral blood leukocytes (PBL) can result in the stable long-term reconstitution of a functional human immune system in mice with severe combined immunodeficiency (SCID)4. Human PBL transplanted to SCID mice increase in number and survive for at least six months; reconstituted mice show spontaneous secretion of human immunoglobulin and a specific human antibody response is induced following immunization with tetanus toxoid. All of the major cell populations present in PBL are found in the lymphoid tissue and blood of SCID recipients, although the relative proportions of B cells, T-cell subsets and monocytes/macrophages in long-term recipients differ from those found in normal PBL and, in mice transplanted with 50 x 106or more PBL from Epstein-Barr virus (EBV)-seropositive donors, EBV-positive B-cell lymphomas often develop. Our results suggest that xenogeneic transplantation of human lymphoid cells into SCID mice may provide a useful model for the study of normal human immune function, the response of the immune system to pathogenic agents and early events in lym-phomagenesis.