Generation of langerhans cell-like dendritic cells from murine fetal skin

The dendritic cell (DC) lineage is comprised of bone marrow-derived cells that are present in small numbers in nonlymphoid as well as lymphoid tissues (1). Nonlymphoid DC, such as epidermal Langerhans cells (LC), display an immature phenotype, i.e., they are capable of acquiring and processing antigen, but express only low levels of MHC antigen and costimulatory molecules and do not effectively initiate primary immune responses. In contrast, interdigitating DC in lymphoid tissue display a mature phenotype, i.e., they have limited phagocytic and antigen-processing capacity, but express high levels of MHC antigen and costimulatory molecules and are very effective stimulators of naive T cells (2). The conceptual link between nonlymphoid and lymphoid organ DC was provided by Schuler et al. several years ago when they demonstrated that epidermal LC cultured in GM-CSF-containing media for several days matured into cells with phenotypic and functional characteristics of interdigitating DC (3). The transformation of immature epidermal LC into mature DC in vitro mimics what occurs in vivo during the migration of epidermal LC to regional lymph nodes. This model has been widely used for studies of LC/DC function.