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STUDY OF XENO-THYMIC TRANSPLANTATUON FOR XENO-GRAFT

异种胸腺移植的研究

基本信息

批准号：
10671235
负责人：
MORIMOTO Takeshi
金额：
$ 2.05万
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：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671235/
关键词：
THYMUS XENO-RAFT NUDE MOUSE RAT OVARY THYROID 胸腺内臓器移植 T細胞ブタウシウサギモルモット

项目摘要

Reconstitution of T cell functions in athymic BALB/c nude mice was investigated after transplantation of embryonic thymus grafts under the renal capsule (TG nude mice). Thymi were obtained from mice, rats, rabbits, hamsters, guinea pigs, swine and cows. All of the grafted thymi grew and formed proper thymic structure with host CD90 positive cells. The TCRβ expression pattern of the lymphocytes in the grafted thymi was quite similar to that of normal mouse thymocytes. Sufficient CD4 positive populations were observed in the peripheral lymphoid organs of all groups of TG nude mice. Plaque-forming cell assay revealed that the TG nude mice had acquired considerable helper T cell functions. Skin grafts from syngeneic mice and thymic donor rat strains were accepted, whereas those from allogeneic mice and the rats of other strains were vigorously rejected. Histological and serological studies, however, showed multiple organ-licalized inflammatory diseases in TG nude mice of all xenogeneic thymus groups, but not with syngeneic or allogeneic thymi. The organs affected were thyroid, the lacrimal, submandibular and sublingual glandsm, the eyes, stomach and ovaries. The incidence of lesions was variable depending on the species of origin of the grafted thymus. Development of autoimmune diseases in TG nude mice was prevented by a single injection of splenic CD4 positive cells from normal BALB/c mice. These results together suggested that the microenvironment of grafted thymi, even if xenogeneic, is able to educate host T cell precursors. However, this reconstitution of function does not always induce tolerance to certain autoantigens, resulting in development of multiple autoimmune lesions.

本文观察了裸鼠肾包膜下移植胚胎胸腺后T细胞功能的重建。胸腺获自小鼠、大鼠、兔、仓鼠、豚鼠、猪和牛。移植胸腺均能正常生长，并与宿主CD 90阳性细胞形成正常胸腺结构。移植胸腺中淋巴细胞TCRβ的表达模式与正常小鼠胸腺细胞十分相似。在所有组的TG裸鼠的外周淋巴器官中观察到足够的CD 4阳性群体。空斑形成细胞分析显示，TG裸鼠获得了相当多的辅助性T细胞功能。同基因小鼠和胸腺供体大鼠品系的皮肤移植物被接受，而异基因小鼠和其他品系的大鼠的皮肤移植物被强烈排斥。然而，组织学和血清学研究显示，所有异种胸腺组的TG裸鼠均出现多种器官化炎性疾病，而同系或同种异体胸腺组则无。受影响的器官有甲状腺、泪腺、下颌下腺和舌下腺、眼睛、胃和卵巢。病变的发生率是可变的，这取决于移植胸腺的种属来源。通过单次注射来自正常BALB/c小鼠的脾CD 4阳性细胞来预防TG裸小鼠中自身免疫性疾病的发展。这些结果共同表明，移植胸腺的微环境，即使是异种的，也能够培养宿主T细胞前体。然而，这种功能的重建并不总是诱导对某些自身抗原的耐受，导致多种自身免疫性病变的发展。