Functions of Thymic Epithelial Cells

在胸腺中的T细胞发育期间，T细胞遇到抗原呈递细胞并进行阳性或阴性选择。识别胸腺基质细胞表面主要组织相容性复合体（MHC）的CD 4 ^+/CD 8 ^+双阳性（DP）细胞存活，而不识别MHC的DP细胞则因凋亡而死亡。对自身抗原应答的DP细胞也通过凋亡而耗尽，然后DP细胞分化为CD 4或CD 8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会在胸腺中发现，这表明凋亡的胸腺细胞必须被清除剂迅速清除。在这项研究中，我们发现CD^<4+>/CD 11b ^+/CD 11 c ^+细胞存在于胸腺中，并且这些CD^<4+>+/CD 11b ^+细胞吞噬凋亡的胸腺细胞的效率比胸腺CD 4/CD 11b ^+细胞以及活化的腹腔巨噬细胞要高得多。随着胸腺的发育，CD 4 ^+/CD 11b ^+细胞沿着变大，而CD 4 ^-/CD 11b ^+细胞则没有观察到这种变化。这些结果有力地表明，胸腺CD 4 ^+/CD 11b ^+细胞是凋亡胸腺细胞的主要清除者。我们还发现，CD 4 ^+/CD 11b ^+细胞来源于未成熟的胸腺细胞，通过与抑瘤素M（OSM）反应性胸腺上皮细胞的相互作用。对OSMR缺陷小鼠的研究表明，OSM对胸腺发育很重要。

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.