Inhibition of maturation and function of dendritic cells by intravenous immunoglobulin.
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.
Bayry
Jagadeesh
J
INSERM U 430 and Université Pierre et Marie Curie, Institut des Cordeliers, Paris, France.
Lacroix-Desmazes
Sébastien
S
Carbonneil
Cedric
C
Misra
Namita
N
Donkova
Vladimira
V
Pashov
Anastas
A
Chevailler
Alain
A
Mouthon
Luc
L
Weill
Bernard
B
Bruneval
Patrick
P
Kazatchkine
Michel D
MD
Kaveri
Srini V
SV
D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology
D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12