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 responses 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 dendritic cells present in lymphoid organs. LC in LCH granulomas intensely expressed B7-1 and B7-2 molecules, whereas normal pulmonary LC and LC accumulating in other pathologic lung disorders did not express these costimulatory 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-1beta and the absence of IL-10) that is known to promote the in vitro differentiation of LC into cells expressing a lymphostimulatory phenotype. Finally, LCH granulomas were the only site where CD154-positive T cells could be identified 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 suggest that therapeutic strategies aimed at modifying the lymphostimulatory phenotype of LC may be useful in the treatment of this disorder.
Tazi
A
A
Institut National de la Santé et de la Recherche Médicale U82, Unité de Formation et de Recherche Xavier Bichat, Paris, France. abdellatif.tazi@avc.ap-hop-paris.fr
Moreau
J
J
Bergeron
A
A
Dominique
S
S
Hance
A J
AJ
Soler
P
P
D000328:Adult; D000368:Aged; D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006646:Histiocytosis, Langerhans-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008024:Ligands; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged
D018122:B7-1 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand