CCR7 signals are essential for cortex-medulla migration of developing thymocytes.
Upon TCR-mediated positive selection, developing thymocytes relocate within the thymus from the cortex to the medulla for further differentiation and selection. However, it is unknown how this cortex-medulla migration of thymocytes is controlled and how it controls T cell development. Here we show that in mice deficient for CCR7 or its ligands mature single-positive thymocytes are arrested in the cortex and do not accumulate in the medulla. These mutant mice are defective in forming the medullary region of the thymus. Thymic export of T cells in these mice is compromised during the neonatal period but not in adulthood. Thymocytes in these mice show no defects in maturation, survival, and negative selection to ubiquitous antigens. TCR engagement of immature cortical thymocytes elevates the cell surface expression of CCR7. These results indicate that CCR7 signals are essential for the migration of positively selected thymocytes from the cortex to the medulla. CCR7-dependent cortex-medulla migration of thymocytes plays a crucial role in medulla formation and neonatal T cell export but is not essential for maturation, survival, negative selection, and adult export of thymocytes.
Ueno
Tomoo
T
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, 3-18-15 Kuramoto, 770-8503, Japan.
Saito
Fumi
F
Gray
Daniel H D
DH
Kuse
Sachiyo
S
Hieshima
Kunio
K
Nakano
Hideki
H
Kakiuchi
Terutaka
T
Lipp
Martin
M
Boyd
Richard L
RL
Takahama
Yousuke
Y
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D017931:DNA Primers; D004801:Eosine Yellowish-(YS); D005434:Flow Cytometry; D005453:Fluorescence; D006416:Hematoxylin; D051379:Mice; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013950:Thymus Gland / Q000254:growth & development / Q000502:physiology*
C515371:Ccr7 protein, mouse; D017931:DNA Primers; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin