Migration of murine epidermal Langerhans cells to regional lymph nodes: engagement of major histocompatibility complex class II antigens induces migration of Langerhans cells.

Abstract

Langerhans cells are resident dendritic cells in the epidermis. Once they are loaded with epicutaneously-delivered antigens, they leave the epidermis and migrate to the regional lymph nodes where they initiate primary T cell responses as antigen-presenting cells. However, the stimulus that initiates such migration remains unknown. Because major histocompatibility complex class II (Ia) antigens on B lymphocytes or monocytic cells have been shown to function as signal transducers, we evaluated the effect of the engagement of Ia antigens on the migration of murine epidermal Langerhans cells. The intradermal injection of an anti-Ia monoclonal antibody (mAb) reduced the density of Langerhans cells in epidermis and produced a dose- and time-dependent increase in the frequency of cells reactive with NLDC145 (Langerhans cell- and dendritic cell-specific mAb) within the regional lymph nodes. Injection of a control mAb had no effect. The NLDC145+ cells that were induced to accumulate in the regional lymph nodes were Ia+, large dendritic cells, some of which were positive for both NLDC145 and F4/80, a phenotype corresponding to that of murine epidermal Langerhans cells. Thus, the engagement of Ia antigens on Langerhans cells by mAb induces the migration of Langerhans cells from the epidermis to the regional lymph nodes. Analysis of these changes in Langerhans cells in vitro may help to reveal the biochemical sequence of events involved in the activation and differentiation of Langerhans cells.