CCR7-mediated migration in the thymus controls γδ T-cell development
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CCR7-mediated migration in the thymus controls γδ T-cell development. / Reinhardt, Annika; Ravens, Sarina; Fleige, Henrike; Haas, Jan D; Oberdörfer, Linda; Łyszkiewicz, Marcin; Förster, Reinhold; Prinz, Immo.
In: EUR J IMMUNOL, Vol. 44, No. 5, 05.2014, p. 1320-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CCR7-mediated migration in the thymus controls γδ T-cell development
AU - Reinhardt, Annika
AU - Ravens, Sarina
AU - Fleige, Henrike
AU - Haas, Jan D
AU - Oberdörfer, Linda
AU - Łyszkiewicz, Marcin
AU - Förster, Reinhold
AU - Prinz, Immo
N1 - © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Movement/physiology
KW - Gene Expression Regulation/genetics
KW - Mice
KW - Mice, Knockout
KW - Receptors, Antigen, T-Cell, gamma-delta/genetics
KW - Receptors, CCR/biosynthesis
KW - Receptors, CCR7/biosynthesis
KW - T-Lymphocytes/cytology
KW - Thymus Gland/cytology
U2 - 10.1002/eji.201344330
DO - 10.1002/eji.201344330
M3 - SCORING: Journal article
C2 - 24500801
VL - 44
SP - 1320
EP - 1329
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 5
ER -
