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CC chemokine receptor 7-dependent and -independent pathways for lymphocyte homing: Modulation by FTY720

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Item Type:Article
Title:CC chemokine receptor 7-dependent and -independent pathways for lymphocyte homing: Modulation by FTY720
Creators Name:Henning, G. and Ohl, H. and Junt, T. and Reiterer, P. and Brinkmann, V. and Nakano, H. and Hohenberger, W. and Lipp, M. and Foerster, R.
Abstract:Cognate interaction of chemokine receptor CCR7 on lymphocytes with its ligands CCL19 and CCL21 expressed on high endothelial venules (HEVs) is essential for effective migration of T and B cells across HEVs into secondary lymphoid organs. Plt mice, which lack expression of CCL19 and CCL21-ser, both ligands for CCR7 on HEVs, as well as CCR7-deficient mice, have a defective cell migration and reduced homing of lymphocytes. FTY720, a novel immunosuppressant, causes a reduction of lymphocytes in peripheral blood and tissues and their sequestration into lymphoid tissues. In this study we demonstrate that FTY720 rescues the homing defect in both CCR7(-/-) mice and plt mice. After FTY720 treatment, the number of CD4(+) and CD8(+) T cells as well as B cells in peripheral blood is reduced while pertussis toxin-sensitive homing into peripheral lymph nodes, mesenteric lymph node, and Peyer's patches is increased. Immunohistology demonstrates that FTY720 enables these cells to enter lymphoid tissue through HEVs. Thus, our data suggest an alternative G-alpha(i)-dependent, CCR7-CCL19/CCL21-independent mechanism for lymphocyte homing through HEVs which is strongly augmented in the presence of FTY720.
Keywords:Lymphocyte Migration, Chemokine Receptor, T Cell, B Cell, Lymphoid Organs, Animals, Mice
Source:Journal of Experimental Medicine
ISSN:0022-1007
Publisher:Rockefeller University Press (U.S.A.)
Volume:194
Number:12
Page Range:1875-1881
Date:17 December 2001
Official Publication:https://doi.org/10.1084/jem.194.12.1875
PubMed:View item in PubMed

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