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CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance

Official URL:https://doi.org/10.1016/j.immuni.2005.12.011
PubMed:View item in PubMed
Creators Name:Kurobe, H. and Liu, C. and Ueno, T. and Saito, F. and Ohigashi, I. and Seach, N. and Arakaki, R. and Hayashi, Y. and Kitagawa, T. and Lipp, M. and Boyd, R.L. and Takahama, Y.
Journal Title:Immunity
Journal Abbreviation:Immunity
Volume:24
Number:2
Page Range:165-177
Date:February 2006
Keywords:Autoimmunity, CCR7 Receptors, Cell Movement, Chemokine Receptors, Dendritic Cells, Epithelial Cells, Immune Tolerance, Leukocyte Chemotaxis, Lysophospholipids, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Signal Transduction, Sphingosine, Thymus Gland, Animals, Mice
Abstract:Immature CD4+CD8+ thymocytes, which are generated in the thymic cortex, are induced upon positive selection to differentiate into mature T lymphocytes and relocate to the thymic medulla. It was recently shown that a chemokine signal via CCR7 is essential for the cortex-to-medulla migration of positively selected thymocytes in the thymus. However, the role of the cortex-to-medulla migration in T cell development and selection has remained unclear. The present study shows that the developmental kinetics and the thymic export of mature thymocytes were undisturbed in adult mice lacking CCR7 or its ligands (CCR7L). The inhibition of sphingosine-1-phosphate-mediated lymphocyte egress from the thymus led to the accumulation of mature thymocytes in the cortex of CCR7- or CCR7L-deficient mice, unlike the accumulation in the medulla of normal mice, thereby suggesting that mature thymocytes may be exported directly from the cortex in the absence of CCR7 signals. However, the thymocytes that were generated in the absence of CCR7 or CCR7L were potent in causing autoimmune dacryoadenitis and sialadenitis in mice and were thus incapable of establishing central tolerance to organ-specific antigens. These results indicate that CCR7-mediated cortex-to-medulla migration of thymocytes is essential for establishing central tolerance rather than for supporting the maturation or export of thymocytes.
ISSN:1074-7613
Publisher:Cell Press (U.S.A.)
Item Type:Article

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