PHAGOCYTOSIS OF ANTIGENS BY LANGERHANS CELLS IN-VITRO

Dendritic cells (DC) isolated from lymphoid tissues are generally thou ght to be nonphagocytic in culture. It has therefore been unclear how these cells could acquire particulate antigens such as microorganisms for initiation of primary immune responses. Lymphoid DC derive in part from cells that have migrated from nonlymphoid tissues, such as Lange rhans cells (LC) of skin. The ability of LC to internalize a variety o f particles was studied by electron, ultraviolet, phase, and different ial interference contrast microscopy, and by two-color flow cytometry. Freshly isolated LC in epidermal cell suspensions phagocytosed the ye ast cell wall derivative zymosan, intact Saccharomyces cerevisiae, rep resentatives of two genera of Gram-positive bacteria, Corynebacterium parvum and Staphylococcus aureus, as well as 0.5-3.5-mum latex microsp heres. During maturation in culture, the phagocytic activity of these cells was markedly reduced. Likewise, freshly isolated splenic DC were more phagocytic than cultured DC for two types of particle examined, zymosan and latex beads. Unlike macrophages, LC did not bind or intern alize sheep erythrocytes before or after opsonization with immunoglobu lin G or complement, and did not internalize colloidal carbon. The rec eptors mediating zymosan uptake by LC were examined. For this particle , C57BL/6 LC were considerably more phagocytic than BALB/c LC and exhi bited 2 reproducible increase in phagocytic activity after 6 h of cult ure followed by a decline, whereas this initial rise did not occur for BALB/c LC. These differential kinetics of uptake were reflected in th e pattern of zymosan binding at 4-degrees-C, and endocytosis of the so luble tracer fluorescein isothiocyanate-mannose-bovine serum albumin a t 37-degrees-C. Zymosan uptake by LC from both strains of mice was inh ibited in the presence of mannan or beta-glucan, although to different extents, but not by antibodies specific for CR3 (CD11b/CD18). These d ata indicate that zymosan uptake by LC can be mediated by a mannose/be ta-glucan receptor(s) that is differentially expressed in the two stra ins of mice and that is downregulated during maturation of LC in cultu re.