Li JiChu, Park JooHung, Foss Deborah, Goldschneider Irving
Department of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
J Exp Med. 2009 Mar 16;206(3):607-22. doi: 10.1084/jem.20082232. Epub 2009 Mar 9.
Many dendritic cells (DCs) in the normal mouse thymus are generated intrathymically from common T cell/DC progenitors. However, our previous work suggested that at least 50% of thymic DCs originate independently of these progenitors. We now formally demonstrate by parabiotic, adoptive transfer, and developmental studies that two of the three major subsets of thymic DCs originate extrathymically and continually migrate to the thymus, where they occupy a finite number of microenvironmental niches. The thymus-homing DCs consisted of immature plasmacytoid DCs (pDCs) and the signal regulatory protein alpha-positive (Sirpalpha(+)) CD11b(+) CD8alpha(-) subset of conventional DCs (cDCs), both of which could take up and transport circulating antigen to the thymus. The cDCs of intrathymic origin were mostly Sirpalpha(-) CD11b(-) CD8alpha(hi) cells. Upon arrival in the thymus, the migrant pDCs enlarged and up-regulated CD11c, major histocompatibility complex II (MHC II), and CD8alpha, but maintained their plasmacytoid morphology. In contrast, the migrant cDCs proliferated extensively, up-regulated CD11c, MHC II, and CD86, and expressed dendritic processes. The possible functional implications of these findings are discussed.
正常小鼠胸腺中的许多树突状细胞（DC）是由胸腺内的常见T细胞/DC祖细胞产生的。然而，我们之前的研究表明，至少50%的胸腺DC独立于这些祖细胞产生。我们现在通过联体生活、过继转移和发育研究正式证明，胸腺DC的三个主要亚群中的两个起源于胸腺外，并持续迁移至胸腺，在那里它们占据有限数量的微环境龛位。归巢至胸腺的DC由未成熟浆细胞样DC（pDC）和传统DC（cDC）的信号调节蛋白α阳性（Sirpα(+)）CD11b(+) CD8α(-)亚群组成，这两种细胞均可摄取循环抗原并将其转运至胸腺。胸腺内起源的cDC大多为Sirpα(-) CD11b(-) CD8α(hi)细胞。迁移至胸腺后，迁移的pDC体积增大，上调CD11c、主要组织相容性复合体II（MHC II）和CD8α，但仍保持其浆细胞样形态。相比之下，迁移的cDC大量增殖，上调CD11c、MHC II和CD86，并表达树突状突起。我们还讨论了这些发现可能的功能意义。
