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Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2002-05-1447.
Submitted May 30, 2002
Accepted August 14, 2002
Inhibition of maturation and function of dendritic cells by intravenous immunoglobulin
Jagadeesh Bayry, Sebastien Lacroix-Desmazes, Cedric Carbonneil, Namita Misra, Vladimira Donkova, Anastas Pashov, Alain Chevailler, Luc Mouthon, Bernard Weill, Patrick Bruneval, Michel D Kazatchkine, and Srini V Kaveri*
INSERM U430 and Universite Pierre et Marie Curie, Hopital Broussais, Paris, France
Laboratoire Immunologie et Immuno-pathologie, Universitaire Angers, Angers, France
Service de Medecine Interne, Hopital Avicenne, Paris, France
Laboratoire Immunologie Biologique, Hopital Cochin, Paris, France
* Corresponding author; email: srini.kaveri{at}brs.ap-hop-paris.fr.
Normal immunoglobulin G for therapeutic use (intravenous immunoglobulin, IVIg) is used in an increasing number of immune-mediated conditions, including acute and chronic/relapsing autoimmune diseases, transplantation and systemic inflammatory disorders. Several mutually non-exclusive mechanisms of action account for the immunoregulatory effects of IVIg. Although IVIg inhibits T cell proliferation and T cell cytokine production, it is not clear whether these effects are directly dependent on effects of IVIg on T cells or via inhibition of antigen presenting cell activity. Here, we examined the effects of IVIg on differentiation, maturation and function of dendritic cells (DC). We show that IVIg inhibits the differentiation and maturation of DC in vitro, and abrogates the capacity of mature DC to secrete IL-12 upon activation, while enhancing IL-10 production. IVIg-induced down-regulation of co-stimulatory molecules associated with modulation of cytokine secretion resulted in inhibition of auto-and allo-reactive T cell activation and proliferation. Modulation of DC maturation and function by IVIg is of potential relevance to its immunomodulatory effects in controlling specific immune responses in autoimmune diseases, transplantation and other immune-mediated conditions.
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