T Cell-Mediated Terminal Maturation of Dendritic Cells: Loss of Adhesive and Phagocytotic Capacities

Dendritic cells (DC) are a specific subset of APC characterized by the potent ability to activate immunologically naive T cells. We have observed previously that the murine epidermis-derived DC line XS52 undergoes a set of profound changes upon Ag-specific interaction with T cells, including IL-1beta; secretion, acquired expression of CD86, and lost expression of CD115 (CSF-1 receptor) and proliferative responsiveness to CSF-1. These changes, which appear to reflect a critical transition during Ag presentation, have been termed T cell-mediated "terminal maturation" of DC. Here we report that XS52 cells also lose their adhesive and phagocytotic capacities during this event. XS52 cells ordinarily adhere to petri dishes and phagocytose latex beads, as has been reported for DC freshly procured from spleen and skin. Importantly, XS52 cells lose both capacities after 3 to 24 h of incubation with HDK-1 T cells (keyhole limpet hemocyanin-specific Th1 clone) or with 5S8 T cells (dinitrobenzene sulfonate-specific Th0 clone) in the presence of Ag. By contrast, incubation with T cells alone or with Ag alone has minimal effects, indicating that this regulation required both T cells and Ag. With respect to mechanisms, several lines of evidence suggest that IFN-γ, which is secreted by T cells, serves as the primary mediator in down-regulating both capacities. Our observations illustrate a unique mechanism by which responding T cells, upon Ag-specific activation by DC, suppress the machinery of Ag uptake through the elaboration of IFN-γ.