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Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2002-05-1447.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 758-765
TRANSFUSION MEDICINE
Inhibition of maturation and function of dendritic cells by
intravenous immunoglobulin
Jagadeesh Bayry,
Sébastien 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
From INSERM U 430 and Université Pierre et Marie
Curie, Institut des Cordeliers, Paris; Laboratoire d'Immunologie et
d'Immuno-pathologie, Universitaire d'Angers; Service de
Médecine Interne, Hôpital Avicenne, Paris; and Laboratoire
d'Immunologie Biologique, Hôpital Cochin, Paris,
France.
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 nonexclusive mechanisms of action account
for the immunoregulatory effects of IVIg. Although IVIg inhibits T-cell
proliferation and T-cell cytokine production, it is unclear whether
these effects are directly dependent on the effects of IVIg on T cells
or they are dependent through the inhibition of antigen-presenting cell activity. Here, we examined the effects of IVIg on differentiation, maturation, and function of dendritic cells (DCs). We show that IVIg
inhibits the differentiation and maturation of DCs in vitro and
abrogates the capacity of mature DC to secrete interleukin-12 (IL-12)
on activation while enhancing IL-10 production. IVIg-induced down-regulation of costimulatory molecules associated with
modulation of cytokine secretion resulted in the inhibition of
autoreactive and alloreactive 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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