The Journal of Experimental Medicine
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Published online 7 May 2001.
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© The Rockefeller University Press, 0022-1007/2001/5/1105/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 9, May 7, 2001 1105-1112

Brief Definitive Report

The Ccr7 Ligand ELC (Ccl19) Is Transcytosed in High Endothelial Venules and Mediates T Cell Recruitment

Espen S. Baekkevolda, Takeshi Yamanakaa, Roger T. Palframanc, Hege S. Carlsena, Finn P. Reinholtb, Ulrich H. von Andrianc, Per Brandtzaega, and Guttorm Haraldsena

a Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway
b Laboratory for Electron Microscopy, Institute of Pathology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway
c The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115
LIIPAT, Rikshos- pitalet, N-0027 Oslo, Norway.47-2307-151147-2307-1494

e.s.bakkevold{at}labmed.uio.no

Lymphocyte homing to secondary lymphoid tissue is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial selectin-mediated tethering and rolling, firm adhesion of lymphocytes requires rapid upregulation of lymphocyte integrin adhesiveness. This step is mediated in part by the HEV-derived chemokine SLC (secondary lymphoid-tissue chemokine, or CCL21) that binds to the CC chemokine receptor (CCR)7 on lymphocytes. However, the CC chemokine ELC (Epstein-Barr virus–induced molecule 1 ligand chemokine, or CCL19) shares the same receptor, and ELC transcripts have been observed in the T cell areas of lymphoid organs. Here, we show that perivascular ELC is transcytosed to the luminal surfaces of HEVs and enables efficient T cell homing to lymph nodes. In situ hybridization on sections of human tonsil showed no ELC mRNA in HEVs, but immunostaining revealed ELC protein in cytoplasmic vesicles of HEV cells. Furthermore, ELC injected into the footpads of mice entered the draining lymph nodes and was presented by HEVs. Finally, intracutaneous injections of ELC in mice lacking functionally relevant ELC and SLC (plt/plt mice) restored T cell trafficking to draining lymph nodes as efficiently as SLC. We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest.

Key Words: chemokines • lymphocyte trafficking • vascular endothelium • lymphoid tissue • plt/plt mice

E.S. Baekkevold and T. Yamanaka contributed equally to this work.

© 2001 The Rockefeller University Press


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