Human lung dendritic cells have an immature phenotype with efficient mannose receptors.
Dendritic cells (DC) can be present at distinct stages of differentiation within the immune system. Sallusto and colleagues have recently described an in vitro culture system suitable for analyzing the maturation processes of DC (Sallusto and colleagues, J. Exp. Med. 1994;179:1109-1118). Monocytes cultured for 6 d in the presence of granulocyte macrophage colony-stimulating factor and interleukin-4 develop into immature DC with a high endocytic capacity but a low capacity to stimulate T cells. When challenged by lipopolysaccharide, these cells upregulate costimulatory molecules, express CD83, and become mature DC. CCR1 and CCR5 chemokine receptors are highly expressed on immature DC and downregulated on mature DC. This in vitro system was used to characterize human lung DC. Lung DC were shown to express some characteristics of in vitro immature DC. These are: (1) low expression of the costimulatory molecules CD40, CD80, and CD86; (2) poor expression of the differentiation marker CD83 and no CD1a; and (3) good capacity to incorporate dextran. Lung DC express moderate levels of CCR1 and CCR5. However, lung DC, like in vitro mature DC, express high levels of major histocompatibility complex Class II molecules, show low expression of CD14 and CD64, and are characterized by their high capacity to stimulate allogeneic T cells to proliferate during mixed leukocyte reactions (MLRs). Although lung DC express low levels of CD80 and CD86, the important role of these costimulatory molecules in inducing high MLR was demonstrated by using blocking antibodies. Therefore, while lung DC have overall a phenotype and an endocytic capacity close to in vitro immature DC, they share, like in vitro mature DC, a powerful capacity to stimulate T cells.
Cochand
L
L
Division of Pneumology, University of Geneva, Geneva, Switzerland.
Isler
P
P
Songeon
F
F
Nicod
L P
LP
D015703:Antigens, CD / Q000096:biosynthesis; D000955:Antigens, T-Independent / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D003911:Dextrans / Q000493:pharmacokinetics; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type; D008168:Lung / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009000:Monocytes / Q000276:immunology; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000955:Antigens, T-Independent; C515300:CCR1 protein, human; D003911:Dextrans; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate