Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D

Chaigne-Delalande B; Li FY; O'Connor GM; Lukacs MJ; Jiang P; Zheng LX; Shatzer A; Biancalana M; Pittaluga S; Matthews HF; Jancel TJ; Bleesing JJ; Marsh RA; Kuijpers TW; Nichols KE; Lucas CL; Nagpal S; Mehmet H; Su HC; Cohen JI; Uzel G; Lenardo MJ

Science, Vol.341, No.6142, 186-191, 2013

DOI10.1126/science.1240094 Export Citation

Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D

Chaigne-Delalande B, Li FY, O'Connor GM, Lukacs MJ, Jiang P, Zheng LX, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, Jancel TJ, Bleesing JJ, Marsh RA, Kuijpers TW, Nichols KE, Lucas CL, Nagpal S, Mehmet H, Su HC, Cohen JI, Uzel G, Lenardo MJ

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.