title: Characterization of expression, cytokine regulation, and effector function of the high affinity IgG receptor Fc gamma RI (CD64) expressed on human blood dendritic cells.
abstract: The mechanisms responsible for efficient sequestration of Ag by cells of the dendritic cell (DC) lineage remain incompletely characterized. One pathway, internalization of Ag-IgG complexes via CD32 (the type II IgG FcR, Fc gamma RII) enhances Ag presentation 100-fold over noncomplexed Ag. Blood leukocytes differentially express two additional IgG FcR, Fc gamma RI (CD64) and Fc gamma RIII (CD16), which may also participate in leukocyte functions such as phagocytosis, Ab-dependent cellular cytotoxicity (ADCC), release of oxygen intermediates, and enhancement of Ag presentation. A phagocytically active form of CD64 was recently demonstrated on human blood DC, but complete functional potential of CD64 on the DC lineage remains undefined. Therefore, highly purified human blood DC (CD33(2)+, CD14-, CD11c2+, HLA-DR3+, CD64+ (CD83+ after overnight culture)) and monocytes (CD33(2)+, CD14(3)+, CD11c2+, HLA-DR+, CD64(2)+, CD83-) were compared for cytokine modulation and effector functions of CD64. Both DC and monocyte CD64 expression was increased by IFN-gamma and IL-10, but while monocyte CD64 was decreased by IL-4, DC CD64 remained unchanged. FcR-mediated functional differences were also evident between the DC and the monocytes. Monocytes generated robust Fc gamma R-dependent superoxide anion release and ADCC activity, while DC failed to release reactive oxygen intermediates and demonstrated minimal ADCC activity, despite apparently normal expression of the gamma-chain subunit and the signaling molecule Syk. In contrast, DC were more efficient than monocytes with respect to T cell activation when Ag was targeted specifically to CD64. These new findings suggest a previously unappreciated potential for CD64 to shape the immune response by dramatically increasing the efficiency with which DC sequester Ag prior to achieving full T cell stimulatory potential.
authors.affiliation: Department of Physiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Fanger
authors.forename: D
authors.initials: D
authors.lastname: Voigtlaender
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Swink
authors.forename: K
authors.initials: K
authors.lastname: Wardwell
authors.forename: J
authors.initials: J
authors.lastname: Fisher
authors.forename: R F
authors.initials: RF
authors.lastname: Graziano
authors.forename: L C
authors.initials: LC
authors.lastname: Pfefferkorn
authors.forename: P M
authors.initials: PM
authors.lastname: Guyre
mesh_terms: D000595:Amino Acid Sequence; D000920:Antibody-Dependent Cell Cytotoxicity; D017951:Antigen Presentation / Q000276:immunology; D001773:Blood Cells / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D004792:Enzyme Precursors / Q000737:chemistry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000737:chemistry; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D000072377:Syk Kinase
chemical_list: D016207:Cytokines; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D013481:Superoxides; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase