Human langerhans cells are more efficient than CD14(-)CD1c(+) dermal dendritic cells at priming naive CD4(+) T cells.
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-gamma and tumor necrosis factor-alpha ) and Th2 (IL-4 and IL-5) cytokines. Moreover, anti-PD-L1 mAb increased the production of IFN-gamma 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.
Furio
Laetitia
L
Clinique Dermatologique, Université de Lyon, Hopital E. Herriot, Lyon, France.
Briotet
Isabelle
I
Journeaux
Alexandra
A
Billard
Hermine
H
Péguet-Navarro
Josette
J
D015703:Antigens, CD / Q000378:metabolism; D018949:Antigens, CD1 / Q000378:metabolism; D060890:B7-H1 Antigen; D023201:CD40 Ligand / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; D018949:Antigens, CD1; D060890:B7-H1 Antigen; C437944:CD1C protein, human; C423236:CD274 protein, human; D006023:Glycoproteins; D007519:Isoantigens; D018950:Lipopolysaccharide Receptors; D023201:CD40 Ligand; D007371:Interferon-gamma