ENTRY INTO AFFERENT LYMPHATICS AND MATURATION IN-SITU OF MIGRATING MURINE CUTANEOUS DENDRITIC CELLS

An important property of dendritic cells (DC), which contributes cruci ally to their strong immunogenic function, is their capacity to migrat e from sites of antigen capture to the draining lymphoid organs, Here we studied in detail the migratory pathway and the differentiation of DC during migration in a skin organ culture model and, for comparison, in the conventional contact hypersensitivity system, We report severa l observations on the capacity of cutaneous DC to migrate in mouse ear skin, (i) Upon application of contact allergens in vivo the density o f Langerhans cells in epidermal sheets decreased, as determined by imm unostaining for major histocompatibility complex class II, ADPase, F4/ 80, CD11b, CD32, NLDC-145/DEC-205, and the cytoskeleton protein viment in, Evaluation was performed by computer assisted morphometry, (ii) Ch emically related nonsensitizing or tolerizing compounds left the densi ty of Langerhans cells unchanged, (iii) Immunohistochemical double-sta ining of dermal sheets from skin organ cultures for major histocompati bility complex class II and CD54 excluded blood vessels as a cutaneous pathway of DC migration, (iv) Electron microscopy of organ cultures r evealed dermal accumulations of DC (including Birbeck granule containi ng Langerhans cells) within typical lymphatic vessels, (v) Populations of migrating DC in organ cultures upregulated markers of maturity (th e antigen recognized by monoclonal antibody 2A1, CD86), but retained i ndicators of immaturity (invariant chain, residual antigen processing function), These data provide additional evidence that during both the induction of contact hypersensitivity and in skin organ culture, Lang erhans cells physically leave the epidermis. Both Langerhans cells and dermal DC enter lymphatic vessels, DC mature while they migrate throu gh the skin.