In vivo study of human xenogeneic immune system by SCID mice GVHD model

SCID小鼠GVHD模型对人类异种免疫系统的体内研究

• 批准号: 05670986
• 负责人: FUJIMORI Keisei
• 金额: $ 1.34万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670986/
• 关键词: SCID mice; GVHD; CB-17; Icr-scid Jcl; hu-PBL-SCID; 照射SCIDマウス; 細胞移入; NK細胞; 細胞移入実験; 細胞浸潤; GVH反応

The use of severe combined immunodeficient (SCID) mice to examine ways to introduce a xenogeneic immune system into SCID mice by taking advantage of the immune deficiency of the mice has provided an animal graft-versus-host disease (GVHD) model to examine the in vivo fanction of transferred human peripheral blood leukocytes (PBL). Transfer of human PBL has been successful or produced acute GVHD,however, the cotroversy remains regarding the capability of human PBL to develop classical symptoms of GVHD.To obtain consistent engraftment with GVHD,SCID mice were pretreated with a combination of total body irradiation (250R) anti-lymphcyte serum (ALS) and anti-asialo GM1 (anti-mouse natural killer cell) antiserum before the intraperitoneal injection of 1 X 10 (6) human PBL.With this protocol, human CD3-positive cells was 1.66-3.36% in the peripheral blood and 2.27-3.67% in the spleen. Human tumor cell lines were implanted subcutaneously or intraperitonealy into the SCID mice to estimate the take rate. The overall take rate was 0% for SCID mice. In our experiment, CB-17/Icr-scid Jcl could not accept any human cells and lines. Mortality at 2 week was 60% (3/5) in the mice bearing human cells after the treatment of irradiation and serum compared with 100% in the control mice. Histologic examination of lymphocytes engraftment of lung liver and duodenum was indistinguishable from normal control in SCID mice. In this context, the cause of death in SCID mice was thought to be the toxic effect of pretreatment rather than GVHD.Although we could not established a GVHD model with SCID mice, we have modified the method of immunoselection of cells which allows a fast positive selection viable T,B lymphocytes.

利用严重联合免疫缺陷(SCID)小鼠研究如何利用小鼠的免疫缺陷将异种免疫系统引入SCID小鼠，为研究移植的人外周血白细胞(PBL)在体内的功能提供了一种动物移植物抗宿主病(GVHD)模型。为了获得与GVHD一致的植入，SCID小鼠在注射1×10(6)人PBL之前，用250R抗淋巴细胞血清(ALS)和抗ASIALO GM1(抗小鼠自然杀伤细胞)抗血清进行联合处理，人CD3阳性细胞在外周血中为1.66-3.36%，在脾中为2.27-3.67%。将人肿瘤细胞系移植到SCID小鼠的皮下或腹膜内，以评估其摄取率。SCID小鼠的总接种率为0%。在我们的实验中，CB-17/ICR-SCID JCL不能接受任何人类细胞和细胞系。照射加血清治疗2周后，荷人细胞组小鼠死亡率为60%(3/5)，对照组为100%。SCID组小鼠肺、肝、十二指肠淋巴细胞移植的组织学检查与正常对照组无明显差别。在这种情况下，SCID小鼠的死亡原因被认为是预处理的毒性作用，而不是GVHD。尽管我们不能用SCID小鼠建立GVHD模型，但我们已经修改了免疫选择细胞的方法，允许快速阳性选择存活的T、B淋巴细胞。