title: 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 (Mg(2+)) 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 Mg(2+) 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 Mg(2+) 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 Mg(2+) in eukaryotic cells.
authors.affiliation: Molecular Development of the Immune System Section, Lymphocyte Molecular Genetics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chaigne-Delalande
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Li
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Connor
authors.forename: Marshall J
authors.initials: MJ
authors.lastname: Lukacs
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Lixin
authors.initials: L
authors.lastname: Zheng
authors.forename: Amber
authors.initials: A
authors.lastname: Shatzer
authors.forename: Matthew
authors.initials: M
authors.lastname: Biancalana
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Helen F
authors.initials: HF
authors.lastname: Matthews
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Jancel
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: Kim E
authors.initials: KE
authors.lastname: Nichols
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Lucas
authors.forename: Sunil
authors.initials: S
authors.lastname: Nagpal
authors.forename: Huseyin
authors.initials: H
authors.lastname: Mehmet
authors.forename: Helen C
authors.initials: HC
authors.lastname: Su
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lenardo
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008274:Magnesium / Q000276:immunology*; D008275:Magnesium Deficiency / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism*; D053632:X-Linked Combined Immunodeficiency Diseases / Q000276:immunology
chemical_list: D027682:Cation Transport Proteins; C509698:MagT1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D008274:Magnesium