Lymphocyte Adhesion to Psoriatic Dermal Endothelium Is Mediated by a Tissue-specific Receptor/Ligand Interaction

Abstract

Dermal lymphocytic infiltrates are characteristic of psoriasis and may be involved in the pathogenesis of the disease. We have utilized an in vitro lymphocyte adherence assay to examine the mechanism(s) mediating lymphocyte migration into psoriatic skin. In this assay, we assessed the binding of lymphocytes overlaid onto frozen biopsy sections of normal and psoriatic skin. Lymphocytes isolated from human blood and rat thoracic duct bound specifically to dermal endothelia in psoriatic plaques but not to those of uninvolved skin from psoriatic patients or skin from normal individuals; analysis of the binding properties of B cells and T lymphocyte subsets revealed a preferential binding of CD4+ T cells compared with CD8+ T cells or B cells. This lymphocyte-endothelial interaction is an energy- and calcium-dependent process and involves surface protein and carbohydrate moieties, requirements similar to those found in lymphocyte interaction with post-capillary high endothelial venules (HEV) in lymphoid tissues. However, preincubation of lymphocytes with antibodies directed against surface molecules mediating adhesion to HEV of peripheral lymph node and gut-associated lymphoid tissue did not interfere with the capacity of lymphophocytes to bind to the skin. The results of this study support the hypothesis that emigration of lymphocytes from vasculature into psoriatic skin is promoted by the presence of specialized endothelia in psoriatic dermis capable of mediating specific lymphocyte-endothelial interactions.