ABSTRACT
The mechanism of the efficacy of Intravenous immunoglobulins (IVIG) in autoimmune and inflammatory diseases is not well understood. This study aimed at understanding mechanisms of IVIG-mediated suppression of effector cell activities of peripheral blood mononuclear cells (PBMC) in antibody-dependent cellular cytotoxicity (ADCC). We were particularly interested in CD56dim NK cells, the main ADCC effector cells in PBMC. Exposure of PBMC to IVIG for at least 48â¯h induced a caspase-3-dependent apoptotic cell death of CD56dim NK cells without affecting CD56bright NK cells. Induction of apoptosis in CD56dim NK cells and concomitant suppression of ADCC effector activities of PBMC was associated with the monomer fraction of IVIG. Moreover, it was independent of IgG sialyation, did not depend on engagement of FcγRIII and could not be mimicked by IVIG (Fab')2 or IVIG Fc preparations. The described effect could contribute to the reduction of peripheral NK cells observed during IVIG therapy in patients.
Subject(s)
Antibody-Dependent Cell Cytotoxicity/drug effects , Apoptosis/drug effects , CD56 Antigen/analysis , Immunoglobulins, Intravenous/pharmacology , Killer Cells, Natural/drug effects , Leukocytes, Mononuclear/immunology , Humans , Killer Cells, Natural/immunology , Receptors, IgG/analysisABSTRACT
West Nile virus (WNV)-neutralizing intravenous immune globulins (IVIG) were fractionated into IgG subclasses, and the contribution of each subclass to in vitro neutralization of and in vivo protection against WNV was evaluated. The results indicate that IgG1 (i) is the main subclass induced following WNV infection of humans, (ii) contained nearly all the in vitro WNV neutralization capacity, and (iii) mediates effector functions in vivo that render it superior to other subclasses in protection against WNV. The importance of human IgG1 indicates that a candidate WNV vaccine should induce an immune response that includes WNV-specific IgG1.
