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

Abstract

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.

CCL19 (ELC) as an adjuvant for DNA vaccination: induction of a TH1-type T-cell response and enhancement of antitumor immunity

“…When injected intracutaneously, CCL19 is able to restore T-cell trafficking to regional lymph nodes in mice lacking functional CCL19 and CCL21. 28 Furthermore, there are data demonstrating that CCL19 is expressed by DC in lymphoid tissues and that it strongly attracts naive T cells. 29,30,31 We therefore postulate that after intramuscular DNA injection, it is mainly CCL19 expression occurring in regional lymph nodes (in DC and other cells), which is responsible for increased recruitment of naive T cells and possibly DC.…”

Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium

“…It is also apparent that syndecan core proteins may be involved in forming membrane rafts, concentrating ligands in membrane microdomains and internalizing ligands in vesicles (6,(67)(68)(69). Chemokine transcytosis and presentation by endothelial cells involve plasmalemmal vesicles (caveolae) and membrane microdomains (the tips of endothelial microvilli) (13,31,70), which suggests a potential role for syndecans in these mechanisms.…”

Dopamine Selectively Induces Migration and Homing of Naive CD8+ T Cells via Dopamine Receptor D3

“…6A) (25). Migration of lymphocytes into the secondary lymphoid tissues is now known to be controlled by the homeostatic chemokines SLC/CCL21 and ELC/CCL19 that are presented on high endothelial venules of the secondary lymphoid tissues (21,(37)(38)(39)(40)(41). In addition, SDF-1/CXCL12 and its receptor CXCR4 are reported to participate in these steps (37,38).…”