Differentiation of Langerhans cells in Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) consists of lesions composed of cells w ith a dendritic Langerhans cell (LC) phenotype. The clinical course of LCH ranges from spontaneous resolution to a chronic and sometimes lethal diseas e. We studied 25 patients with various clinical forms of the disease. In bo ne and chronic lesions, LCH cells had immature phenotype and function. They coexpressed LC antigens CD1a and Langerin together with monocyte antigens CD68 and CD14. Class II antigens were intracellular and LCH cells almost ne ver expressed CD83 or CD86 or dendritic cell (DC)-Lamp, despite their CD40 expression. Consistently, LCH cells sorted from bone lesions (eosinophilic granuloma) poorly stimulated allogeneic T-cell proliferation in vitro, Stri kingly, however, in vitro treatment with CD40L induced the expression of me mbrane class II and CD86 and strongly increased LCH cell allostimulatory ac tivity to a level similar to that of mature DCs, Numerous interieukin-10-po sitive (IL-10(+)), Langerin(-), and CD68(+) macrophages were found within b one and lymph node lesions. In patients with self-heating and/or isolated c utaneous disease, LCH cells had a more mature phenotype, LCH cells were fre quently CD14(-) and CD86(+), and macrophages were rare or absent, as were I L-10-expressing cells. We conclude that LCH cells in the bone and/or chroni c forms of the disease accumulate within the tissues in an immature state a nd that most probably result from extrinsic signals and may be induced to d ifferentiate toward mature DCs after CD40 triggering. Drugs that enhance th e in vivo maturation of these immature DCs, or that induce their death, may be of therapeutic benefit. (Blood. 2001;97:1241-1248) (C) 2001 by The Amer ican Society of Hematology.