Evidence that langerhans cells in adult pulmonary langerhans cell histiocytosis are mature dendritic cells: Importance of the cytokine microenvironment

Because Langerhans cells (LC) in peripheral tissues are generally "immature " cells with poor lymphostimulatory activity, the contribution of immune re sponses initiated by LC to the pathogenesis of pulmonary LC histiocytosis ( LCH) has been uncertain. In this study we demonstrate that LC accumulating in LCH granulomas are phenotypically similar to mature lymphostimulatory de ndritic cells present in lymphoid organs. LC in LCH granulomas intensely ex pressed B7-1 and B7-2 molecules, whereas normal pulmonary LC and LC accumul ating in other pathologic lung disorders did not express these costimulator y molecules. The presence of B7(+) LC in LCH granulomas was associated with the expression in these lesions, but not at other sites in the lung, of a unique profile of cytokines (presence of GM-CSF, TNF-alpha, and IL-1 beta a nd the absence of IL-10) that is known to promote the in vitro differentiat ion of LC into cells expressing a lymphostimulatory phenotype, Finally, LCH granulomas were the only site where CD154-positive T cells could be identi fied in close contact with LC intensely expressing CD40 Ags, Taken together , these results strongly support the idea that an abnormal immune response initiated by LC may participate in the pathogenesis of pulmonary LCH, and s uggest that therapeutic strategies aimed at modifying the lymphostimulatory phenotype of LC may be useful in the treatment of this disorder.