title: The CMRF58 antibody recognizes a subset of CD123hi dendritic cells in allergen-challenged mucosa.
abstract: CD123(hi) CD11c(-) dendritic cells (CD123(hi) DC) are a distinct subset of human DC present in bone marrow, blood, lymphoid organs, and peripheral tissues. Pathogen stimulation, cytokine, or CD40 ligation induces CD123(hi) DC maturation, involving a shift from their innate immune to cognate antigen-presenting functions. In this study, we revealed that blood CD123(hi) DC in the presence of cytokine (granulocyte macrophage-colony stimulating factor and interleukin-3) undergo progressive, step-wise maturation through an "early" stage, delineated by expression of the antigen detected by the new monoclonal antibody CMRF58 (CD123(hi)CMRF58(+)CD40(-)CD86(-)CD83(-)) to the "late" stage with costimulatory antigen expression (CD123(hi)CMRF58(+)CD40(+)CD86(+)CD83(+/-)). In this early stage, cytokine-maintained CD123(hi) DC do not display changes in their morphology, no longer produce interferon-alpha (IFN-alpha) in response to bacteria, and develop the capacity to induce proliferation and polarization of allogeneic T cells. CD123(hi)CMRF58(+) DC, phenotypically similar to in vitro cytokine-maintained CD123(hi) DC, were not detected in tonsil but are present in allergen-challenged nasal mucosa of allergic individuals. Thus, CD123(hi) DC in certain tissue environments such as allergen-challenged nasal mucosa share a common CD123(hi)CMRF58(+) phenotype with in vitro cytokine-maintained blood CD123(hi) DC characterized by lack of IFN-alpha production.
authors.affiliation: Mater Medical Research Institute, Aubigny Place, Raymond Terrace, South Brisbane, Queensland 4101, Australia. svuckovic@mmri.mater.org.au
authors.forename: Slavica
authors.initials: S
authors.lastname: Vuckovic
authors.forename: Dalia
authors.initials: D
authors.lastname: Khalil
authors.forename: Nicola
authors.initials: N
authors.lastname: Angel
authors.forename: Frode
authors.initials: F
authors.lastname: Jahnsen
authors.forename: Iona
authors.initials: I
authors.lastname: Hamilton
authors.forename: Amanda
authors.initials: A
authors.lastname: Boyce
authors.forename: Barry
authors.initials: B
authors.lastname: Hock
authors.forename: Derek N J
authors.initials: DN
authors.lastname: Hart
mesh_terms: D000485:Allergens / Q000276:immunology* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity / Q000276:immunology*; D039521:CD11c Antigen / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007159:Immunologic Tests; D016130:Immunophenotyping; D053650:Interleukin-3 Receptor alpha Subunit; D007962:Leukocytes / Q000276:immunology; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology*; D014066:Palatine Tonsil / Q000276:immunology; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis*
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D039521:CD11c Antigen; D016207:Cytokines; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D016185:Receptors, Interleukin-3