CCR7-mediated migration in the thymus controls γδ T-cell development

Eur J Immunol. 2014 May;44(5):1320-9. doi: 10.1002/eji.201344330. Epub 2014 Mar 7.


αβ T-cell development and selection proceed while thymocytes successively migrate through distinct regions of the thymus. For γδ 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 γδ T-cell development. γδ 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 γδ T-cell output in CCR7-deficient mice. In vitro, CCR7-deficient precursors showed normal γδ T-cell development. Immunohistology revealed that CCR7 and CCR9 expression was important for γδ T-cell localization within thymic medulla or cortex, respectively. However, γδ T-cell motility was unaltered in CCR7- or CCR9-deficient thymi. Together, our results suggest that proper intrathymic localization is important for normal γδ T-cell development.

Keywords: C-C chemokine receptor CCR7; C-C chemokine receptor CCR9; intrathymic migration; γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Mice
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, CCR / biosynthesis
  • Receptors, CCR / genetics
  • Receptors, CCR / immunology
  • Receptors, CCR7 / biosynthesis
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism


  • CC chemokine receptor 9
  • Ccr7 protein, mouse
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR
  • Receptors, CCR7