Functions of Thymic Epithelial Cells

在胸腺中T细胞的发育过程中，T细胞会遇到抗原提呈细胞，并受到阳性或阴性选择。识别胸腺基质细胞表面主要组织相容性复合体(MHC)的CD4~+/CD8~+双阳性(DP)细胞存活，而不识别MHC的DP细胞死亡。对自身抗原有反应的DP细胞也会因凋亡而耗尽，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细胞发育过程中被凋亡所消除。然而，胸腺中通常不会发现凋亡的胸腺细胞，这表明必须通过清道夫迅速消除凋亡的胸腺细胞。在这项研究中，我们发现胸腺中存在CD^&lt；4+&gt；/CD11b^+/CD11c^+细胞，这些CD^&lt；4+&gt；+/CD11b^+细胞吞噬凋亡的胸腺细胞比胸腺CD4/CD11b^+细胞以及活化的腹膜巨噬细胞要有效得多。随着胸腺发育，CD4^+/CD11b^+细胞逐渐变大，而CD4^-/CD11b^+细胞则无明显变化。这些结果有力地表明，胸腺CD4^+/CD11b^+细胞是胸腺细胞凋亡的主要清除者。我们还发现，未成熟的胸腺细胞通过与OSM反应的胸腺上皮细胞相互作用而获得了CD4~+/CD11b~+细胞。对OSMR缺陷小鼠的研究表明，OSM对胸腺发育具有重要作用。

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.