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

被引：253

作者：

Chaigne-Delalande, Benjamin ^{[1
]}

Li, Feng-Yen ^{[1
,2
]}

O'Connor, Geraldine M. ^{[3
]}

Lukacs, Marshall J. ^{[1
]}

Jiang, Ping ^{[1
]}

Zheng, Lixin ^{[1
]}

Shatzer, Amber ^{[4
]}

Biancalana, Matthew ^{[1
]}

Pittaluga, Stefania ^{[5
]}

Matthews, Helen F. ^{[1
]}

Jancel, Timothy J. ^{[6
]}

Bleesing, Jack J. ^{[7
]}

Marsh, Rebecca A. ^{[7
]}

Kuijpers, Taco W. ^{[8
]}

Nichols, Kim E. ^{[9
]}

Lucas, Carrie L. ^{[1
]}

Nagpal, Sunil ^{[10
]}

Mehmet, Huseyin ^{[10
]}

Su, Helen C. ^{[11
]}

Cohen, Jeffrey I. ^{[3
]}

Uzel, Gulbu ^{[12
]}

Lenardo, Michael J. ^{[1
]}

机构：

[1] NIAID, Mol Dev Immune Syst Sect, Lymphocyte Mol Genet Unit, Immunol Lab,NIH, Bethesda, MD 20892 USA

[2] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA

[3] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21702 USA

[4] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA

[5] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA

[6] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA

[7] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA

[8] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands

[9] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[10] Merck Res Labs, Resp & Immunol Div, Boston, MA USA

[11] NIAID, Immunol Dis Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA

[12] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA

来源：

SCIENCE | 2013年 / 341卷 / 6142期

关键词：

KILLER-CELLS; MAGNESIUM; MAGT1; ACTIVATION; COSTIMULATION; SURVEILLANCE; METABOLISM; GROWTH; TRPM7;

D O I：

10.1126/science.1240094

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：186 / 191

页数：6

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