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Functions of Thymic Epithelial Cells

胸腺上皮细胞的功能

基本信息

批准号：
14370109
负责人：
MIYAJIMA Atsushi
金额：
$ 8.9万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370109/
关键词：
thymus macrophage denritic cells apoptosis epithelial cells T cell cytokine antigen 免疫リンパ球

项目摘要

During T cell development in the thymus, T cells encounter antigen-presenting cells and are subjected to either positive or negative selection. CD4^+/CD8^+ double positive (DP) cells that recognize major histocompatibility complex (MHC) on the surface of thymic stromal cells survive, whereas those DP cells that do not recognize MHC die by apoptosis. DP cells that respond to self-antigens are also depleted by apoptosis, and then DP cells differentiate to either CD4 or CD8 single positive (SP) cells. Thus, a vast majority of thymocytes is eliminated during T cell development by apoptosis. However, apoptotic thymocytes are not usually found in the thymus, indicating that apoptotic thymocytes must be eliminated rapidly by scavengers. In this study, we found that CD^<4+>/CD11b^+/CD11c^+ cells were present in the thymus and that these CD^<4+>+/CD11b^+ cells phagocytosed apoptotic thymocytes much more efficiently than thymic CD4/CD11b^+ cells as well as activated peritoneal macrophages. CD4^+/CD11b^+ cells became larger along with thymus development, while no such change was observed in CD4^-/CD11b^+ cells. These results strongly suggest that thymic CD4^+/CD11b^+ cells are major scavengers of apoptotic thymocytes. We also found that CD4^+/CD11b^+ cells were derived from the immature thymocytes through the interaction with Oncostatin M (OSM) responsive thymic epithelial cells. Studies on OSMR deficient mice revealed that OSM is important for the thymic development.

在胸腺的T细胞发育过程中，T细胞遇到抗原呈递细胞，并受到阳性或阴性选择。CD4^+/CD8^+双阳性（DP）细胞能识别胸腺基质细胞表面的主要组织相容性复合体（MHC）而存活，而不能识别MHC的DP细胞则因凋亡而死亡。对自身抗原有反应的DP细胞也会被凋亡耗尽，然后DP细胞分化为CD4或CD8单阳性（SP）细胞。因此，绝大多数胸腺细胞在T细胞发育过程中通过凋亡被消除。然而，凋亡的胸腺细胞通常不存在于胸腺中，这表明凋亡的胸腺细胞必须被清道夫迅速清除。在这项研究中，我们发现胸腺中存在CD^<4+>+/CD11b^+ /CD11c^+细胞，并且这些CD^<4+>+/CD11b^+细胞比胸腺CD4/CD11b^+细胞和活化的腹膜巨噬细胞更有效地吞噬凋亡的胸腺细胞。CD4^+/CD11b^+细胞随着胸腺的发育而变大，而CD4^-/CD11b^+细胞则无此变化。这些结果强烈提示胸腺CD4^+/CD11b^+细胞是胸腺细胞凋亡的主要清除者。我们还发现CD4^+/CD11b^+细胞来源于未成熟胸腺细胞，通过与Oncostatin M （OSM）应答的胸腺上皮细胞相互作用。对OSMR缺陷小鼠的研究表明，OSMR对胸腺发育有重要作用。