Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells.

Abstract

Langerhans cells (LC)' are leukocytes that are distributed in the suprabasal region of squamous epithelia, particularly skin. LC undergo marked changes when epidermal cell suspensions are prepared by a standard trypsinization protocol and placed in culture for 1-3 d. Several cell surface markers (Fc receptors, the F4/80 antigen, membrane ATPase, and nonspecific esterase) decrease substantially (1, 2), while others (class I and II products of the MHC) increase (3). When accessory function for primary T-dependent immune responses is quantitated, the activity of the LC population increases some 10-30-fold (1, 4). Therefore LC seem to mature immunologically in bulk epidermal culture and acquire most of the features of lymphoid dendritic cells.Because LC maturation leads to the development of accessory function for primary immune responses, this process may contribute to the sensitization phase of cell-mediated immunity . Here, we asked whether maturation is autonomous, or ifexogenous cells and factors are required . We developed a panning technique to enrich the trace LC population from freshly dissociated mouse epidermis. When this was done, the viability and function of cultured LC was dependent upon factors that were found in the medium of keratinocyte cultures, as well as stimulated macrophages and T cells . We will describe these experiments and the identification of granulocyte/macrophage colony-stimulating factor (GM-CSF) as the principal if not exclusive mediator for the production of functioning LC.

Comparison of the Accessory Activity of Murine Peritoneal Cavity Macrophage Derived Dendritic Cells and Peritoneal Cavity Macrophages in a Mixed Lymphocyte Reaction.

“…Similar work on DC from mouse intestinal lamina propria and pig Peyer's patches [21,20,27,40], as well as studies of DC from the human colonic lamina propria demonstrated the presence of cells with potent stimulatory activity in the allogeneic MLR. In contrast, Langerhans' cells are weak stimulators of the allogeneic MLR upon initial isolation [9], but in the presence of GM-CSF and IL-1, in vitro rapidly mature into potent MLR stimulators [5,41]. Variations in levels of cytokine production in the epidermis and the intestine may account for the differences in maturity of DC at the two sites.…”

Dendritic cells: Understanding immunogenicity

“…When the LC were purified, it became evident that granulocyte macrophage stimulating factor (GM-CSF) was essential for LC maturation (Fig. 2) [50]. Then specific protein antigens were tested by another Tyrolean, Nikolaus Romani, who made a second striking observation.…”

Contact allergy, irritancy and ‘danger’

“…The cytokines that give Langerhans cells an immunostimulatory morphology, namely GMCSF, IL-1 and TNFa, are also produced by irritants (24)(25)(26). One could postulate that without these cytokines the Langerhans cells would not be able to activate a sensitization process, and that any antigen presentation would be 'inefficient' and therefore lead to tolerance.…”