Exposure of NK cells to intravenous immunoglobulin induces IFNγ release and degranulation but inhibits their cytotoxic activity

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2009-12, Vol.133 (3), p.393-401
• Main Authors: Jacobi, Christian, Claus, Maren, Wildemann, Brigitte, Wingert, Sabine, Korporal, Mirjam, Römisch, Jürgen, Meuer, Stefan, Watzl, Carsten, Giese, Thomas
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Antigens, CD - blood; Antigens, CD - immunology; Autoimmune Diseases - immunology; Biological and medical sciences; CD107a; Cell Degranulation - drug effects; Cell Degranulation - immunology; Cytolytic activity; Cytotoxicity, Immunologic - immunology; Dose-Response Relationship, Immunologic; Fc-gammaRIII; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granzymes - blood; Granzymes - immunology; Humans; IFNγ; Immunoglobulins, Intravenous - pharmacology; Interferon-gamma - blood; Interferon-gamma - immunology; IVIg; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Multiple Sclerosis - blood; Multiple Sclerosis - immunology; Natural Killer cells; Perforin - blood; Perforin - immunology; Peripheral Nervous System Diseases - blood; Peripheral Nervous System Diseases - immunology
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.09.006

Abstract The mechanisms underlying the modulation of Natural Killer (NK) cell functions by intravenous immunoglobulin (IVIg) are poorly understood. Using an ex vivo whole blood assay system we demonstrate that IVIg suppresses NK cell cytotoxicity. This was paralleled by IVIg-induced degranulation of CD56bright , CD16positive NK cells, reduced expression of CD16 and elevated IFNγ release. To assess whether these findings also occur in vivo we analyzed whole blood before and after IVIg therapy of patients. Following IVIg treatment the number of NK cells in peripheral blood dropped significantly. We observed reduced CD16 expression, elevated IFNγ−amounts in plasma, reduced NK cell cytotoxicity, and granzyme B release into the plasma, confirming our in vitro data. These effects on the functions of NK cells describe a novel immunomodulatory effect of IVIg. The in vitro assays employed here could represent informative test systems to monitor effects of in vivo IVIg treatment at an individual level.