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Development of in Vitro Assay System for the Analysis of Transplanted Bone Marrow Cell Rejection

移植骨髓细胞排斥分析体外检测系统的开发

基本信息

批准号：
01570206
负责人：
SHIMAMURA Kazuo
金额：
$ 0.45万
依托单位：
Tokai 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：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570206/
关键词：
Bone Marrow Transplantation Hemopoietic Histocompatibility NK Cell Bone Marrow Progenitor Splenic Stromal Cell Mouse in vitro Hybrid resistance CFUーGM CFU-M

项目摘要

In addition to alloantigens, recipients reject the hemopoietic cells by recognition of surface structures expressed specifically on the hemopoietic cells, when the hemopoietic cells transplanted from a parental donor to F_1 hybrid of other allogeneic recipients. This specific structures called hemopoietic histocompatibility (Hh) are recognized by cells similar to natural killer cells. Molecular structures of Hh antigens, detection of effector cells and the mechanism by which cells bearing these structures are rejected are remained unanswered because most of the experimental system for examining hemopoietic rejection are in vivo assay. The purposes of this project is to make in vitro model of hemopoietic resistance in which donor hemopoietic cells could be eliminated by recognition of their Hh antigens and to clarify the rejection mechanism. We already detected the followings in lastyear : 1) Neither the lineage nor the degree of commitment or differentiation of hemopoietic cells affect … More their expression of Hh antigens. 2) Elimination of grafted progenitors from host spleen commences 3 hours after the transplantation and less than 10 % of progenitors are remained functional by 24 hour. 3) Severity of the rejection is not necessarily due to the difference of allospecificity between hosts and donors. Understanding these evidences, we developed in vitro model of hemopoietic resistance and clarified the followings : 1) Effector cells mediating elimination of hemopoietic progenitors were coenriched with NK activity but not with T cells after passing nylon wool column and applying Percoll density gradient. 2) Suppression of hemopoietic colony growth was abolished by the cytotoxic treatment of effector cells with anti-asial GM1.3) Hemopoietic progenitors in broad range of differentiation and commitment were susceptible in this in vitro assay. And 4) In the presence of host stromal cells, stimulation not but suppression of donor colony growth was observed. From the results, we concluded that suppression of donor hemopoietic colony growth was observed in vitro in the specificity similar to in vivo assay. However, the in vitro elimination of donor hemopoietic progenitors was much weaker than that observed in vivo assay system. Less

除了同种异体抗原外，当将亲代供体的造血细胞移植到其他异体受体的F_1杂交体时，受体还会通过识别造血细胞特异性表达的表面结构来排斥造血细胞。这种被称为造血组织相容性（Hh）的特殊结构被类似于自然杀伤细胞的细胞识别。Hh抗原的分子结构、效应细胞的检测以及携带这些结构的细胞被排斥的机制仍然没有答案，因为大多数用于检查造血排斥的实验系统都是体内试验。本课题的目的是建立通过识别供体造血细胞的Hh抗原来清除供体造血细胞的体外造血耐药模型，并阐明其排斥机制。我们在去年已经检测到以下情况：1)造血细胞的谱系、承诺或分化程度都不影响…更多的是Hh抗原的表达。2)移植后3小时开始从宿主脾脏中清除移植物祖细胞，不到10%的祖细胞在24小时内仍保持功能。3)排斥反应的严重程度并不一定是由于宿主和供体异体特异性的差异。在此基础上，我们建立了体外造血阻力模型，明确了以下结论：1)介导造血祖细胞清除的效应细胞通过尼龙羊毛柱和Percoll密度梯度后，与NK细胞活性共富集，而与T细胞活性不共富集。2)抗asial gm3效应细胞的细胞毒处理消除了对造血集落生长的抑制。1.3)在体外实验中，广泛分化的造血祖细胞易受影响。4)在宿主基质细胞存在的情况下，供体菌落的生长不是受到刺激，而是受到抑制。从实验结果可以看出，体外实验对供体造血集落生长的抑制具有与体内实验相似的特异性。然而，供体造血祖细胞的体外清除比体内检测系统弱得多。少