Molecular mechanisms underlying lymphocyte-specific cell trafficking into lymph nodes-Functional analysis of genes specifically expressed in high endothelial venules (HEV)

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We have successfully isolated endothelial cells from HEV (HEV cells) of peripheral and mesenteric lymph nodes of mice and constructed HEV-specific 3'-end cDNA libraries. We then randomly sequenced about 1,500 cDNA clones from each library and compared the obtained nucleotide sequences with those found in 30 different cDNA libraries similarly obtained from other tissues and also with those registered in the EST database. From this analysis, we found several molecules selectively expressed by HEV cells but not normal endothelial cells. They include mac25/TAF/PSF, SGP-2, DARC, leucine-rich α2 glycoprotein and Ig-hepta. In addition, a few chemokines such as SLC, ELC, BLC, fractalkine, KC and lymphotactin are expressed by HEV at mRNA and protein levels. These chemokines except KC can attract selective lymphocyte subsets in vitro, and hence are strategically useful for recruiting these subsets into lymph nodes. In addition, in collaboration with Prof.M.Minoru of La Jolla, we have successfully cloned a novel GlcNAc-6-O-sulfotransferase selectively expressed inHEV.This enzyme is essential for the formation of an L-selectiin binding sugar moiety, 6-sulfo sialyl Lewis X, and is likely to play a crucial role in the L-selectin-dependent lymphocyte homing into lymph nodes.