Cellular basis of XMEN

Patients with XMEN immunodeficiency have mutation of the gene encoding the Mg²⁺ transporter MAGT1 that results in decreased concentrations of free intracellular Mg²⁺, immunosuppression, chronic infection with Epstein-Barr virus (EBV) and neoplasia. In Science, Lenardo and colleagues investigate the cellular and molecular basis for the poor control of EBV in XMEN. In addition to the known defects in TCR signaling, cytotoxic T lymphocytes (CTLs) and NK cells from patients with XMEN have poor lytic ability ascribed to their lower expression of the stimulatory receptor NKG2D. Mg²⁺ supplementation normalizes intracellular Mg²⁺ concentrations, NKG2D expression and the killing activity of both NK cells and CTLs. Similarly, treatment of patients with XMEN by Mg²⁺ supplementation increases NKG2D expression on CTLs, which coincides with fewer EBV⁺ B cells. These studies therefore identify a specific role for free intracellular Mg²⁺ and suggest a method for treating certain immunodeficiencies.

Science 341, 186–191 (2013)