Normal monocyte-derived dendritic cell function in patients with Langerhans-cell-histiocytosis

BACKGROUND: Langerhans cell histiocytosis (LCH) is a histiocytic disease, characterized by the lesional accumulation of dendritic Langerhans cells together with T cells and eosinophils. The cause of this disease is unknown. Langerhans cells are bone marrow-derived dendritic cells (DCs), which can develop from CD34(+) hematopoietic progenitor cells as well as from monocytes. PROCEDURE: To test whether LCH patients have a general functional defect present in cells of their DC lineage, we generated immature DCs by culturing monocytes from nine patients with single- or multisystem LCH with GM-CSF and IL-4, and analyzed their phenotype and function before and after an in vitro maturation stimulus. Immature DCs were analyzed for their phenotype and cytokine production, DCs matured in response to TNF-alpha plus PGE(2) were analyzed for their phenotype, their stimulatory capacity in MLR, cell aggregation, and activation-induced apoptosis. RESULTS: In summary, no difference was found between both immature as well as mature DCs generated from patients and controls regarding the expression of CD1a, CD80, CD86, MHC class I, and MCH class II antigens. Similarly, no difference was found regarding IL-10, -12, and TNF-alpha production, as well as regarding cell aggregation and apoptosis in response to external stimuli. CONCLUSIONS: The absence of gross functional abnormalities in DCs generated from monocytes from patients with LCH makes the existence of a severe functional defect affecting all cells of the DC lineage in these patients unlikely.