Exposure of NK cells to intravenous immunoglobulin induces IFN gamma release and degranulation but inhibits their cytotoxic activity.
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 CD56(bright), CD16(positive) NK cells, reduced expression of CD16 and elevated IFN gamma 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 IFN gamma-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.
Jacobi
Christian
C
Institute for Immunology, Department of Neurology, University of Heidelberg, INF 305, 69120 Heidelberg, Germany.
Claus
Maren
M
Wildemann
Brigitte
B
Wingert
Sabine
S
Korporal
Mirjam
M
Römisch
Jürgen
J
Meuer
Stefan
S
Watzl
Carsten
C
Giese
Thomas
T
D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D053804:Granzymes / Q000097:blood / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology; D054353:Perforin / Q000097:blood / Q000276:immunology; D010523:Peripheral Nervous System Diseases / Q000097:blood / Q000276:immunology
D015703:Antigens, CD; D016756:Immunoglobulins, Intravenous; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes