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Microenvironment for thymocyte differentiation, selection and clonal elimination

胸腺细胞分化、选择和克隆消除的微环境

基本信息

批准号：
07407066
负责人：
ITOH Tsunetoshi
金额：
$ 3.26万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07407066/
关键词：
Thymus Thymocytes Differentiation Selection Clonal deletion Microenvironment Apoptosis Cell death

项目摘要

We obtained following conclusions through the 3-years' project entitled "Microenvironment for thymocyte differentiation, selection and clonal elimination".1. The pattern of cell deaths in the thymus and in the lymph nodes, where thymocytes are clonally deleted or affinity maturation takes place with B cells in germinal centers, respectively, was demonstrated not to be apoptosis. In the thymus and at germinal centers, thymocytes or B cells die by pyknosis. It is thus urgently necessary to reconsider what the apoptosis is and what the significance of clonal deletion if it is not accomplished by apoptosis in the thymus.2. Severe and massive thymocyte death due to steroid administration has long been believed to be apoptosis. Careful morphological examination of in vivo thymus clearly revealed that even after steroid treatment, thymocytes died by pyknosis, and immediately after they died by pyknosis they were engulfed by cortical macrophages.3.Plain electron microscopy on FACS-sorted thymocytes based on FLS (cell size) and surface markers identified five morphologically distinct subpopulations possibly at different differentiation stages. This analysis would be extremely useful for future in situ examination of thymocytes for pursuing their differentiation pathway within the thymus.4. Immunological tolerance was successfully established by injecting BALB/c thymic epithelial cell line (IT-76MHC) into allogeneic mouse thymuses (C3H). Mechanisms remain to be elucidated.5. Two different macrophage subsets were recognized in mouse thymus in terms of their location, surface phenotypes, morphology and functions. This finding would consequently lead to more precise investigation of the thymic microenvironment.

通过3年的“胸腺细胞分化、选择和克隆消除的微环境”项目，我们得到了以下结论。在胸腺和淋巴结中，分别发生胸腺细胞克隆缺失或与生发中心的B细胞发生亲和成熟的细胞死亡模式被证明不是细胞凋亡。在胸腺和生发中心，胸腺细胞或B细胞死于固缩。因此，迫切需要重新思考什么是细胞凋亡，如果克隆缺失不是通过胸腺细胞凋亡完成的，那么克隆缺失又有什么意义。长期以来，类固醇引起的胸腺细胞严重和大量死亡被认为是细胞凋亡。对体内胸腺的仔细形态学检查清楚地显示，即使在类固醇治疗后，胸腺细胞仍因固缩而死亡，并在固缩死亡后立即被皮质巨噬细胞吞噬。基于FLS（细胞大小）和表面标记物的facs分类胸腺细胞的普通电子显微镜鉴定出可能处于不同分化阶段的5个形态不同的亚群。这一分析对今后胸腺细胞的原位检查和胸腺内分化途径的探索具有重要意义。通过将BALB/c胸腺上皮细胞系（IT-76MHC）注射到同种异体小鼠胸腺（C3H）成功建立免疫耐受。机制仍有待阐明。两种不同的巨噬细胞亚群在小鼠胸腺中被识别，它们的位置、表面表型、形态和功能。这一发现将导致对胸腺微环境更精确的研究。