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THE ESTABLISHING OF THE IMMUNE SYSTEM OF THE scid MOUSE BY THE TRANSPLANTATION OF THE XENOGENEIC IMMUNE STEM CELLS

异种免疫干细胞移植建立scid小鼠免疫系统

基本信息

批准号：
09670247
负责人：
TAGUCHI Osamu
金额：
$ 1.79万
依托单位：
Aichi Cancer Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670247/
关键词：
XENO-GRAFT IMMUNE STEM CELL TYMUS scid MOUSE NUDE RAT GVHD

项目摘要

Because the lymphocyte stem cell has a malfunction, no population of both T and B cells exists in the lymphoid organs of scid (scid/scid) mouse. However the thymus is equipped with the normal organization. Therefore, when transplanting the bone-barrow cells of nude (rnu/rnu) rat to the scid mouse (rat BMT scid mouse), the lymphocytes of the donor origin immigrate into the thymus. Those lymphocytes get to express rat CD3, CD4, CD8 and TCR antigens like the normal rat thymocytes do. The T cell population of the rat origin emerged to the peripheral lymphoid organs, and B cells of rat origin which can produce immunoglobulins emerged there at the same time. These evidences show that the immune system of rat origin can grow sufficiently in the scid mouse. On the other hand, when transplanting the thymic lobes of the 15th of embryonic rats under the kidney capsule of scid mouse, the lobes grow. The immature T cell population which existed in the grafts developed there and emerges to the periphery as the functional T cells. Then, this mouse falls into GVHD after several months of the rat thymus graft and dies. At the rat BMT scid mouse, neither GVHD nor localized autoimmune diseases developed and the long-range survival is possible. We gave the rat BMT scid mouse a foreign antigen (SRBC) and examined immune function but the reaction was very weak. This phenomenon is peculiar, because both the expression patterns of TCR of T cells and IgG of B cells in rat BMT scid mouse are as those of normal rat. When injecting the spleen cells of the rat BMT scid mouse into nude rat, the decrease of the weight is remarkable from 3 months to 5 months after the treatment and the GVHD-like disease occurred. The rat BMT scid mouse is the model which is extremely useful to study education effects to the T cell of the thymus.

由于淋巴细胞干细胞功能异常，SCID(SCID/SCID)小鼠的淋巴器官中不存在T、B细胞群。然而，胸腺配备了正常的组织。因此，将裸大鼠(RNU/RNU)的骨髓细胞移植到SCID小鼠(大鼠BMT SCID小鼠)体内时，供体来源的淋巴细胞迁移到胸腺。这些淋巴细胞可以像正常大鼠胸腺细胞一样表达大鼠CD3、CD4、CD8和TCR抗原。大鼠来源的T细胞群出现在外周淋巴器官中，同时在那里出现了能产生免疫球蛋白的大鼠来源的B细胞。这些证据表明，大鼠来源的免疫系统可以在SCID小鼠体内充分生长。而将第15胎大鼠的胸腺小叶移植到SCID小鼠的肾被膜下，小叶生长。移植物中存在的未成熟T细胞群在移植物中发育，并以功能性T细胞的形式出现在周围。然后，在大鼠胸腺移植几个月后，这只小鼠陷入移植物抗宿主病并死亡。在大鼠骨髓移植SCID小鼠中，既没有发生移植物抗宿主病，也没有发生局限性自身免疫性疾病，并且有可能长期存活。我们给大鼠骨髓移植SCID小鼠注射了外源抗原(SRBC)，并检测了免疫功能，但反应很弱。这种现象是特殊的，因为大鼠BMT-SCID小鼠T细胞TCR和B细胞免疫球蛋白G的表达模式与正常大鼠相似。将大鼠BMT-SCID小鼠的脾细胞注射到裸鼠体内，治疗后3个月至5个月体重显著下降，出现GVHD样病。大鼠骨髓移植SCID小鼠是研究胸腺T细胞教育效应的非常有用的模型。