Witt Colleen M, Raychaudhuri Subhadip, Schaefer Brian, Chakraborty Arup K, Robey Ellen A
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
PLoS Biol. 2005 Jun;3(6):e160. doi: 10.1371/journal.pbio.0030160. Epub 2005 May 3.
Development of many vertebrate tissues involves long-range cell migrations. In most cases, these migrations have been inferred from analysis of single time points and the migration process has not been directly observed and quantitated in real time. In the mammalian adult thymus, immature CD4+ CD8+ double-positive (DP) thymocytes are found in the outer cortex, whereas after T cell antigen receptor (TCR) repertoire selection, CD4+ CD8- and CD4- CD8+ single-positive (SP) thymocytes are found in the central medulla. Here we have used two-photon laser-scanning microscopy and quantitative analysis of four-dimensional cell migration data to investigate the movement of thymocytes through the cortex in real time within intact thymic lobes. We show that prior to positive selection, cortical thymocytes exhibit random walk migration. In contrast, positive selection is correlated with the appearance of a thymocyte population displaying rapid, directed migration toward the medulla. These studies provide our first glimpse into the dynamics of developmentally programmed, long-range cell migration in the mammalian thymus.
许多脊椎动物组织的发育涉及远距离细胞迁移。在大多数情况下，这些迁移是通过对单个时间点的分析推断出来的，迁移过程尚未被实时直接观察和定量。在成年哺乳动物胸腺中，未成熟的CD4+CD8+双阳性（DP）胸腺细胞位于外皮质，而在T细胞抗原受体（TCR）库选择后，CD4+CD8-和CD4-CD8+单阳性（SP）胸腺细胞位于中央髓质。在这里，我们使用双光子激光扫描显微镜和对四维细胞迁移数据的定量分析，实时研究胸腺细胞在完整胸腺叶内通过皮质的运动。我们发现，在阳性选择之前，皮质胸腺细胞表现出随机游走迁移。相反，阳性选择与一群向髓质快速、定向迁移的胸腺细胞的出现相关。这些研究让我们首次了解了哺乳动物胸腺中发育程序控制的远距离细胞迁移的动态过程。
