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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2441-2443.
Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-04-1325.
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Submitted April 7, 2004
Accepted June 9, 2004
Common variable immunodeficiency is associated with defective functions of dendritic cells
Jagadeesh Bayry, Sebastien Lacroix-Desmazes, Michel D Kazatchkine, Lionel Galicier, Yves Lepelletier, David Webster, Yves Levy, Martha M Eibl, Eric Oksenhendler, Olivier Hermine, and Srini V Kaveri*
Institut des Cordeliers, INSERM Unite 430, Paris, France
Department of Clinical Immunopathology, Hopital Saint Louis, Paris, France
Department of Hematology and Centre National de la Recherche Scientifique Unite Mixte de Recherche 8603, Hopital Necker, Paris, France
Department of Immunology, Royal Free Medical School, London, United Kingdom
Service Immunologie Clinique, Hopital Henri Mondor, Creteil, France
Immunology Outpatient Clinic, Vienna, Austria
* Corresponding author; email: srini.kaveri{at}u430.bhdc.jussieu.fr.
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 DC play a central role in the development of adaptive immunity. We demonstrate that DC from CVID patients display severely perturbed differentiation, maturation and function, and expressed markedly reduced levels of the co-stimulatory molecules that are critical for T-cell stimulation. Patients DC induced weak proliferation of allogeneic T-cells and produced significantly low amounts of IL-12 upon CD40 signalling. Multiple defects in the immune system, including malfunctioning of DC, 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.
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