title: Common variable immunodeficiency is associated with defective functions of dendritic cells.
abstract: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and defects in T-cell functions that could be primary or secondary. We addressed whether CVID is associated with impairment in the dendritic cell (DC) compartment, as DCs play a central role in the development of adaptive immunity. We demonstrate that DCs from CVID patients display severely perturbed differentiation, maturation, and function, and express markedly reduced levels of the costimulatory molecules that are critical for T-cell stimulation. Patients' DCs induced weak proliferation of allogeneic T cells and produced significantly low amounts of interleukin-12 (IL-12) upon CD40 signaling. Multiple defects in the immune system, including malfunctioning of DCs, appear to be prominent features of CVID patients. Impairment in both the innate and adaptive compartments of the immune system may thus cumulatively account for the inability of CVID patients to eradicate pathogens through conventional immune pathways, thus resulting in an increased risk for recurrent bacterial infections.
authors.affiliation: INSERM U430, Institut des Cordeliers, 15, rue de l'Ecole de Médecine, 75006 Paris, France. srini.kaveri@u430.bhdc.jussieu.fr
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Michel D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Yves
authors.initials: Y
authors.lastname: Lepelletier
authors.forename: David
authors.initials: D
authors.lastname: Webster
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Martha M
authors.initials: MM
authors.lastname: Eibl
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
mesh_terms: D002454:Cell Differentiation; D002455:Cell Division; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D018664:Interleukin-12