CD44-HYALURONATE INTERACTION MEDIATES IN-VITRO LYMPHOCYTE BINDING TO THE WHITE-MATTER OF THE CENTRAL-NERVOUS-SYSTEM

The cell adhesion molecule CD44 is expressed in the central nervous sy stem, especially on glial cells in the white matter, the extracellular matrix of which also contains one of its ligands, hyaluronate. We inv estigated the role of CD44 and hyaluronate in the adhesion of human pe ripheral blood lymphocytes to myelinated areas of cerebellum by an in vitro binding assay. Hermes-1 epitope, which recognizes the hyaluronat e binding site of CD44, and Hermes-3 epitope, involved in lymphocyte b inding to mucosal high endothelial venules, were both immunohistochemi cally expressed in the white matter. No immunoreactivity was observed with mAb Var3.1, which sees variant forms of CD44 containing the exon v6 encoding region. The molecular weight analysis showed that CD44 of the white matter was identical to the major 90 kD form of CD44 present on lymphocytes. The binding of both T and B lymphocytes was significa ntly inhibited by pretreatment of both cells and sections with mAb Her mes-1 but not with Hermes-3. Digestion of the sections and/or lymphocy tes with hyaluronidase also reduced lymphocyte binding. These findings implicate that CD44-hyaluronate mediates lymphocyte adhesion to the w hite matter and this interaction may be involved in the pathogenesis o f inflammations and lymphomas of the central nervous system.