Human Langerhans Cells Are More Efficient Than CD14−CD1c+ Dermal Dendritic Cells at Priming Naive CD4+ T Cells

• Published in: Journal of investigative dermatology Vol. 130; no. 5; pp. 1345 - 1354
• Main Authors: Furio, Laetitia, Briotet, Isabelle, Journeaux, Alexandra, Billard, Hermine, Péguet-Navarro, Josette
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-05-2010; Nature Publishing Group; Elsevier Limited
• Subjects: Antigens, CD - metabolism; Antigens, CD1 - metabolism; B7-H1 Antigen; Biological and medical sciences; CD40 Ligand - pharmacology; Cell Communication - immunology; Cell Differentiation - immunology; Cell Division - immunology; Cell Movement - immunology; Dermatology; Down-Regulation - immunology; Glycoproteins - metabolism; Humans; Immunophenotyping; Interferon-gamma - pharmacology; Isoantigens - immunology; Langerhans Cells - cytology; Langerhans Cells - immunology; Langerhans Cells - metabolism; Lipopolysaccharide Receptors - metabolism; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Medical sciences; Th1 Cells - cytology; Th1 Cells - immunology; Th2 Cells - cytology; Th2 Cells - immunology; Human; Dendritic cell; Langerhans cell; Derm; Dermatology; T-Lymphocyte
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2009.424

Few data are available regarding the role of human skin dendritic cells (DCs) in driving T-cell responses. In this study we analyzed the relative capacity of Langerhans cells (LCs) and dermal CD14−CD1c+ DCs (DDCs) to trigger naive CD4+ T-cell proliferation and differentiation. DC subsets were purified after a 2-day migration from epidermis and dermis of the same skin sample. Migratory LCs showed far more activated phenotype than CD1c+DDCs and distinct expression of new molecules of the B7 family; when compared with LCs, CD1c+DDCs showed higher PD-L1 and lower inducible co-stimulator ligand (ICOS-L) expression. As expected, CD1c+DDCs showed lower allostimulatory property than LCs, a process that was partly reversed by anti-PD-L1 mAb. LCs were significantly more efficient than CD1c+DDCs at inducing allogeneic naive CD4+ T cells to secrete both T helper cell 1 (Th1; IFN-γ and tumor necrosis factor-α ) and Th2 (IL-4 and IL-5) cytokines. Moreover, anti-PD-L1 mAb increased the production of IFN-γ by both LC- and CD1c+DDC-stimulated T cells. Globally, these results argue for a preponderant role of human LCs in inducing naive CD4+ T-cell priming. Low expression of co-stimulatory molecules together with high expression of PD-L1 might limit the efficiency of CD1c+DDCs at inducing naive CD4+ T-cell proliferation and secretion of cytokines.