HUMAN CUTANEOUS DENDRITIC CELLS MIGRATE THROUGH DERMAL LYMPHATIC VESSEL CULTURE MODEL

The capacity to migrate from peripheral tissues, where antigen is enco untered, to lymphoid organs, where the primary immune response is init iated, is crucial to the immunogenic function of dendritic cells (DC), The skin is a suitable tissue to study migration, DC were observed to gather in distinct nonrandom arrays (''cords'') in the dermis upon cu lture of murine whole skin explants, It is assumed that cords represen t lymphatic vessels, Using a similar organ culture model with human sp lit-thickness skin explants, we investigated migration pathways in hum an skin. We made the following observations, 1) Spontaneous emigration of Langerhans cells took place in skin cultured for 1-3 d, Nonrandom distribution patterns of strongly major histocompatibility complex cla ss II-expressing DC (cords) occurred in cultured dermis, A variable, y et high (> 50%) percentage of these DC coexpressed the Birbeck granule -associated antigen ''Lag.'' Ultrastructurally, the cells corresponded to mature DC, 2) Electron microscopy proved that the dermal structure s harboring the accumulations of DC (i.e., cords) were typical lymph v essels, Moreover, markers for blood endothelia (monoclonal antibody PA L-E, Factor VIII-related antigen) and markers for cords (strong major histocompatibility complex class II expression on nonrandomly arranged , hairy-appearing cells) were expressed in a mutually exclusive patter n, 3) On epidermal sheets we failed to detect gross changes in the lev els of expression of adhesion molecules (CD44, CD54/ ICAM-1, E-cadheri n) on keratinocytes in the course of the culture period, The reactivit y of a part of the DC in the dermal cords with Birbeck granule-specifi c monoclonal antibody ''Lag'' suggests that the migratory population i s composed of both epidermal Langerhans cells and dermal DC, We conclu de that this organ culture model may prove helpful in resolving pathwa ys and mechanisms of DC migration.