ANTIBODIES AGAINST SIALOPHORIN (CD43) ENHANCE THE CAPACITY OF DENDRITIC CELLS TO CLUSTER AND ACTIVATE T-LYMPHOCYTES

CD43 is a leukocyte membrane glycoprotein rich in negatively charged s ialic acid residues that may act as an anti-adhesion molecule, In this study, we analyzed the expression and function of CD43 on epidermal L angerhans cells (LC) and dendritic cells derived from adherent periphe ral blood monocytes treated with granulocyte-macrophage CSF and IL-4 ( Mo-DC), Both freshly isolated LC (fLC) and Mo-DC expressed uniformly h igh amounts of membrane CD43, with levels unchanged in 48-h cultured L C or in TNF-alpha-treated Mo-DC, When fLC or Mo-DC were transiently pr eincubated with anti-CD43 mAb or neuraminidase, they formed much large r clusters with T cells as compared with cells incubated with control mAb, Moreover, a significantly increased proliferation of naive alloge neic T cells in a primary MLR assay was induced, Anti-CD43-treated Mo- DC also presented tetanus toroid to primed T cells more efficiently. I mmunofluorescence and immunogold electron microscopy showed that follo wing Ab cross-linking and warming to 37 degrees C, CD43 is progressive ly removed from the cell surface and is internalized within endosomes and vacuoles, In addition, fLC and Mo-DC incubated with anti-CD43 mAb increased expression of HLA-DR, ICAM-1, B7-1, B7-2, CD40, and CD83 aft er 24 h, and this was partially prevented by culturing cells in the pr esence of cycloheximide, We thus postulate that membrane CD43, other t han serving as anti-adhesion molecule, can mediate activation signals in immature DC, leading to augmented expression of adhesion/costimulat ory molecules and Ag-presenting function.