IVIG induces apoptotic cell death in CD56dim NK cells resulting in inhibition of ADCC effector activity of human PBMC

Publication date: Available online 31 October 2018

Source: Clinical Immunology

Author(s): Sebastian Bunk, Padmapriya Ponnuswamy, Azra Trbic, Mantas Malisauskas, Heinz Anderle, Alfred Weber, Josenato Ilas, Anna M. Winkler, H. Arno Butterweck, Wolfgang Teschner, Friedrich Scheiflinger, Corinna Hermann, Birgit M. Reipert

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 CD56^dim NK cells, the main ADCC effector cells in PBMC. Exposure of PBMC to IVIG for at least 48 h induced a caspase-3-dependent apoptotic cell death of CD56^dim NK cells without affecting CD56^bright NK cells. Induction of apoptosis in CD56^dim 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.

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