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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.

来源于造血干细胞的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），并且对自身抗原具有高亲和力的T细胞被耐受化（阴性选择）。这些选择是基于它们的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.骨髓-长期培养的骨髓（LTBM）细胞的使用为研究T细胞迁移到胸腺之前的早期分化提供了相关的细胞来源。我们对无胸腺nde小鼠和1 pr/1 pr小鼠的研究表明，LTBM细胞中TcR基因的异常表达，提示这些小鼠BM中的T细胞前体可能在数量和/或质量上与正常小鼠不同.胸腺-辐射骨髓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。我们已经发现，在辐射骨髓嵌合体的胸腺中，具有能够识别宿主和供体表型的TcR的T细胞都被删除。外周淋巴组织-在移植胎儿胸腺的裸鼠中研究了耐受诱导的细胞基础。胸腺上皮细胞有能力诱导对MHCII类抗原的耐受，但对MLS编码的抗原不耐受。