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

A Reinhardt, S Ravens, H Fleige… - European Journal of …, 2014 - Wiley Online Library
A Reinhardt, S Ravens, H Fleige, JD Haas, L Oberdörfer, M Łyszkiewicz, R Förster, I Prinz
European Journal of Immunology, 2014Wiley Online Library
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 …
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.
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