Greiner D L, Shultz L D, Rossini A A, Mordes J P, Handler E S, Rajan T V
Department of Pathology, University of Connecticut Health Center, Farmington 06030.
J Clin Invest. 1991 Aug;88(2):717-9. doi: 10.1172/JCI115359.
Mice homozygous for the mutation "severe combined immune deficiency" (C.B17-scid/scid) lack functional T and B lymphocytes and readily accept tumor xenografts. Partial lymphohemopoietic scid/human and mouse/rat chimeras have been described, but complete chimerization with thymic engraftment and generation of donor-origin thymocytes has not been achieved. We now report that low-dose irradiation permits the engraftment of BB rat fetal liver stem cells in scid recipients. We observed that BB rat fetal liver cells injected into irradiated scid mice establish a rat hemopoietic system in the scid mouse bone marrow and populate the scid mouse thymus. These stem cells generated rat-origin thymocytes that migrated to the scid mouse spleen, a peripheral lymphoid organ. Finally, we found that xenogeneic chimeras created using fetal liver cells from the abnormal (lymphopenic, diabetes prone) subline of BB rats recapitulated both the quantitative and phenotypic abnormalities of the donor rat. Xenogeneic lymphohemopoietic chimeras established in scid mice may provide a powerful new tool in the study of immune system development and autoimmunity.
“严重联合免疫缺陷”(C.B17-scid/scid)突变的纯合子小鼠缺乏功能性T和B淋巴细胞,并且容易接受肿瘤异种移植。部分淋巴细胞造血的scid/人类和小鼠/大鼠嵌合体已被描述,但尚未实现胸腺植入和供体来源胸腺细胞生成的完全嵌合。我们现在报告,低剂量辐射允许BB大鼠胎肝干细胞植入scid受体。我们观察到,注入经辐射的scid小鼠体内的BB大鼠胎肝细胞在scid小鼠骨髓中建立了大鼠造血系统,并在scid小鼠胸腺中定植。这些干细胞产生了源自大鼠的胸腺细胞,这些胸腺细胞迁移到scid小鼠脾脏(一个外周淋巴器官)。最后,我们发现,使用来自BB大鼠异常(淋巴细胞减少、易患糖尿病)亚系的胎肝细胞创建的异种嵌合体重现了供体大鼠的数量和表型异常。在scid小鼠中建立的异种淋巴细胞造血嵌合体可能为免疫系统发育和自身免疫研究提供一个强大的新工具。