CCR7-mediated migration in the thymus controls.d T- cell development

T-cell development and selection proceed while thymocytes successively migrate through distinct regions of the thymus. For T cells, the interplay of intrathymic migration and cell differentiation is less well understood. Here, we crossed C-C chemokine receptor (CCR)7-deficient (Ccr7(-/-)) and CCR9-deficient mice (Ccr9(-/-)) to mice with a TcrdH2BeGFP reporter background to investigate the impact of thymic localization on T-cell development. T-cell frequencies and numbers were decreased in CCR7-deficient and increased in CCR9-deficient mice. Transfer of CCR7- or CCR9-deficient BM into irradiated C57BL/6 WT recipients reproduced these phenotypes, pointing toward cell-intrinsic migration defects. Monitoring recent thymic emigrants by intrathymic labeling allowed us to identify decreased thymic T-cell output in CCR7-deficient mice. In vitro, CCR7-deficient precursors showed normal T-cell development. Immunohistology revealed that CCR7 and CCR9 expression was important for T-cell localization within thymic medulla or cortex, respectively. However, T-cell motility was unaltered in CCR7- or CCR9-deficient thymi. Together, our results suggest that proper intrathymic localization is important for normal T-cell development.