Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D.

Science (New York, N.Y.) (2013-07-13)
Benjamin Chaigne-Delalande, Feng-Yen Li, Geraldine M O'Connor, Marshall J Lukacs, Ping Jiang, Lixin Zheng, Amber Shatzer, Matthew Biancalana, Stefania Pittaluga, Helen F Matthews, Timothy J Jancel, Jack J Bleesing, Rebecca A Marsh, Taco W Kuijpers, Kim E Nichols, Carrie L Lucas, Sunil Nagpal, Huseyin Mehmet, Helen C Su, Jeffrey I Cohen, Gulbu Uzel, Michael J Lenardo

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.

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