Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D
Abstract
The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium (Mg2+) concentrations. Individuals with genetic deficiencies in MAGT1 have high levels of Epstein-Barr virus (EBV) and a predisposition to lymphoma. We show that decreased intracellular free Mg2+ causes defective expression of the natural killer activating receptor NKG2D in natural killer (NK) and CD8+ T cells and impairs cytolytic responses against EBV. Notably, magnesium supplementation in MAGT1-deficient patients restores intracellular free Mg2+ and NKG2D while concurrently reducing EBV-infected cells in vivo, demonstrating a link between NKG2D cytolytic activity and EBV antiviral immunity in humans. Moreover, these findings reveal a specific molecular function of free basal intracellular Mg2+ in eukaryotic cells.
- Publication:
-
Science
- Pub Date:
- July 2013
- DOI:
- 10.1126/science.1240094
- Bibcode:
- 2013Sci...341..186C
- Keywords:
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- IMMUNOLOGY Immunology, Genetics, Cell-Biology