Analysis of molecular mechanisms of T cell differentiation

T细胞分化的分子机制分析

基本信息

批准号：
62480167
负责人：
YOSHIKAI Yasunobu
金额：
$ 4.22万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

T cell precursors derived from hematopoietic stem cells proliferate and differentiate in thymus, where T cells with self-MHC specificities are positively selected (positive selection) and T cells with a high affinities for self-antigens are tolerized(negative selection). These selections are carried out on the basis of their T cell receptors (TcR). To elucidate the molecular mechanism of T cell differentiation, we have investigated the expression of TcR gene in bone marrow(BM), thymus and peripheral lymphoid tissues of mice.1. BM --- The use of the long-term cultured bone marrow (LTBM) cells provided a pertinent source of cells for investigating the early phase of T cell differentiation before migration to the thymus. Our study with athymic nde mice and 1pr/1pr mice indicated abnormal rearrangememnts of TcR genes in the LTBM cells, suggesting that T cell precursors in BM of these mice may be different in quantity and/or quality from those in normal mice.2. Thymus --- Radiation BM chimeras have been used as an experimental model for investigation of mechanisms of selective events in thymxis of adult mice. We have found that both T cells bearing TcR capable of recognizing host- and donor phenotypes are deleted in the thymus of radiation BM chimeras.3. Peripheral lymphoid tissues --- The cellular basis of tolerant induction has been investigated in nude mice grafted with fetal thymus. Thymic epithelium have a capacity to induce tolerance to MHC class II but not to Mls-encoded antigens.

源自造血干细胞的 T 细胞前体在胸腺中增殖和分化，其中具有自身 MHC 特异性的 T 细胞被阳性选择（阳性选择），而对自身抗原具有高亲和力的 T 细胞被耐受（阴性选择）。这些选择是根据其 T 细胞受体 (TcR) 进行的。为了阐明T细胞分化的分子机制，我们研究了TcR基因在小鼠骨髓、胸腺和外周淋巴组织中的表达情况。 1． BM --- 长期培养的骨髓 (LTBM) 细胞的使用为研究迁移到胸腺之前 T 细胞分化的早期阶段提供了相关的细胞来源。我们对无胸腺nde小鼠和1pr/1pr小鼠的研究表明LTBM细胞中TcR基因的异常重排，表明这些小鼠BM中T细胞前体的数量和/或质量可能与正常小鼠不同。2．胸腺——辐射BM嵌合体已被用作研究成年小鼠胸腺选择性事件机制的实验模型。我们发现，携带能够识别宿主和供体表型的TcR的T细胞在辐射BM嵌合体的胸腺中被删除。3．外周淋巴组织——已在移植胎儿胸腺的裸鼠中研究了耐受诱导的细胞基础。胸腺上皮能够诱导对 MHC II 类的耐受，但不能诱导对 Mls 编码的抗原的耐受。