title: CCR7-mediated migration in the thymus controls γδ T-cell development.
abstract: 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.
authors: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors: Annika
authors: A
authors: Reinhardt
authors: Sarina
authors: S
authors: Ravens
authors: Henrike
authors: H
authors: Fleige
authors: Jan D
authors: JD
authors: Haas
authors: Linda
authors: L
authors: Oberdörfer
authors: Marcin
authors: M
authors: Łyszkiewicz
authors: Reinhold
authors: R
authors: Förster
authors: Immo
authors: I
authors: Prinz
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054388:Receptors, CCR / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: C119309:CC chemokine receptor 9; C515371:Ccr7 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054388:Receptors, CCR; D054400:Receptors, CCR7
keywords: C-C chemokine receptor CCR7; C-C chemokine receptor CCR9; intrathymic migration; γδ T cells