The Journal of Experimental Medicine
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Published 3 November 2003. doi:10.1084/jem.20030057
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© Rockefeller University Press, 0022-1007/2003/11/1289 $5.00
The Journal of Experimental Medicine, Volume 198, Number 9, 1289-1300

Lymphocyte–HEV Interactions in Lymph Nodes of a Sulfotransferase-deficient Mouse

Annemieke van Zante1, Jean-Marc Gauguet2, Annette Bistrup1, Durwin Tsay1, Ulrich H. von Andrian2 and Steven D. Rosen1

1 Department of Anatomy, Program in Immunology, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143
2 The CBR Institute for Biomedical Research, Inc., Department of Pathology, Harvard Medical School, Boston, MA 02115

Address correspondence to Steven D. Rosen, Box 0452, University of California, San Francisco, CA 94122. Phone: (415) 476-1579; Fax: (415) 476-4845; email: sdr{at}itsa.ucsf.edu

The interaction of L-selectin expressed on lymphocytes with sulfated sialomucin ligands such as CD34 and GlyCAM-1 on high endothelial venules (HEV) of lymph nodes results in lymphocyte rolling and is essential for lymphocyte recruitment. HEC-GlcNAc6ST–deficient mice lack an HEV-restricted sulfotransferase with selectivity for the C-6 position of N-acetylglucosamine (GlcNAc). HEC-GlcNAc6ST-/- animals exhibit faster lymphocyte rolling and reduced lymphocyte sticking in HEV, accounting for the diminished lymphocyte homing. Isolated CD34 and GlyCAM-1 from HEC-GlcNAc6ST-/- animals incorporate ~70% less sulfate than ligands from wild-type animals. Furthermore, these ligands exhibit a comparable reduction of the epitope recognized by MECA79, a function-blocking antibody that reacts with L-selectin ligands in a GlcNAc-6-sulfate–dependent manner. Whereas MECA79 dramatically inhibits lymphocyte rolling and homing to lymph nodes in wild-type mice, it has no effect on HEC-GlcNAc6ST-/- mice. In contrast, in vitro rolling on purified GlyCAM-1 from HEC-GlcNAc6ST-/- mice, although greatly diminished compared with that on the wild-type ligand, is inhibited by MECA79. Our results demonstrate that HEC-GlcNAc6ST contributes predominantly, but not exclusively, to the sulfation of HEV ligands for L-selectin and that alternative, non-MECA79–reactive ligands are present in the absence of HEC-GlcNAc6ST.

Key Words: lymphocyte homing • L-selectin • sulfotransferase • endothelium • MECA79


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