Hyaluronan-independent adhesion of CD44H(+) and CD44v10(+) lymphocytes to dermal microvascular endothelial cells and keratinocytes

We have recently shown the CD44 variant isoform 10 (CD44v10) to be expresse d on reactive as well as malignant cutaneous lymphocytes; however, the func tional consequences of CD44v10 expression on lymphocytes are not elucidated . By using appropriately transfected lymphatic cells we analyzed the role o f CD44v10 on lymphocytes in cell-matrix adhesion and homotypic and heteroty pic cell-cell adhesion assays. Despite a low binding affinity to hyaluronan , CD44v10-expressing lymphocytes exhibited heterotypic cell-cell adhesion t o inflamed dermal microvascular endothelium and keratinocytes, as indicated by Stamper-Woodruff assays on tissue sections of delayed type hypersensiti vity reactions and adhesion assays with cultured keratinocytes and cytokine -stimulated human dermal microvascular endothelial cells. Antibody-blocking assays excluded interaction of CD44v10 with the principal CD44 ligand hyal uronan as well as involvement of selectins. or integrins in these heterotyp ic cell-cell adhesion assays. In contrast, cellular aggregation assays with fluorescence-labeled CD44v10- and CD44H-expressing lymphocytes revealed ho motypic CD44v10/CD44v10 binding as well as binding of CD44v10 with CD44H. H eterotypic cell-cell adhesion assays with ultraviolet-A-irradiated CD44v-ne gative cytokine-stimulated endothelial cells demonstrated binding kinetics of CD44v10-expressing lymphocytes paralleling those of endothelial CD44H ex pression. These results imply that a hyaluronan-independent CD44v10/CD44H-m ediated pathway is involved in lymphocyte infiltration into the dermis and epidermis of inflamed skin and suggest modulation of CD44H expression on in flamed dermal microvascular endothelium as a mechanism of ultraviolet-A-ind uced therapeutic effects on the skin.