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

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

doi:10.1126/science.1240094

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

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. CohenGulbu Uzel, Michael J. Lenardo

Research output: Contribution to journal › Article › Academic › peer-review

274 Citations (Scopus)

Abstract

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

Original language	English
Pages (from-to)	186-191
Journal	Science
Volume	341
Issue number	6142
DOIs	https://doi.org/10.1126/science.1240094
Publication status	Published - 2013

Access to Document

10.1126/science.1240094

Cite this

Chaigne-Delalande, B., Li, F.-Y., O'Connor, G. M., Lukacs, M. J., Jiang, P., Zheng, L., Shatzer, A., Biancalana, M., Pittaluga, S., Matthews, H. F., Jancel, T. J., Bleesing, J. J., Marsh, R. A., Kuijpers, T. W., Nichols, K. E., Lucas, C. L., Nagpal, S., Mehmet, H., Su, H. C., ... Lenardo, M. J. (2013). Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D. Science, 341(6142), 186-191. https://doi.org/10.1126/science.1240094

@article{f62b849418354606ab94317310edc580,

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 (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",

author = "Benjamin Chaigne-Delalande and Feng-Yen Li and O'Connor, {Geraldine M.} and Lukacs, {Marshall J.} and Ping Jiang and Lixin Zheng and Amber Shatzer and Matthew Biancalana and Stefania Pittaluga and Matthews, {Helen F.} and Jancel, {Timothy J.} and Bleesing, {Jack J.} and Marsh, {Rebecca A.} and Kuijpers, {Taco W.} and Nichols, {Kim E.} and Lucas, {Carrie L.} and Sunil Nagpal and Huseyin Mehmet and Su, {Helen C.} and Cohen, {Jeffrey I.} and Gulbu Uzel and Lenardo, {Michael J.}",

year = "2013",

doi = "10.1126/science.1240094",

language = "English",

volume = "341",

pages = "186--191",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6142",

}

Chaigne-Delalande, B, Li, F-Y, O'Connor, GM, Lukacs, MJ, Jiang, P, Zheng, L, 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 2013, 'Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D', Science, vol. 341, no. 6142, pp. 186-191. https://doi.org/10.1126/science.1240094

TY - JOUR

T1 - Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D

AU - Chaigne-Delalande, Benjamin

AU - Li, Feng-Yen

AU - O'Connor, Geraldine M.

AU - Lukacs, Marshall J.

AU - Jiang, Ping

AU - Zheng, Lixin

AU - Shatzer, Amber

AU - Biancalana, Matthew

AU - Pittaluga, Stefania

AU - Matthews, Helen F.

AU - Jancel, Timothy J.

AU - Bleesing, Jack J.

AU - Marsh, Rebecca A.

AU - Kuijpers, Taco W.

AU - Nichols, Kim E.

AU - Lucas, Carrie L.

AU - Nagpal, Sunil

AU - Mehmet, Huseyin

AU - Su, Helen C.

AU - Cohen, Jeffrey I.

AU - Uzel, Gulbu

AU - Lenardo, Michael J.

PY - 2013

Y1 - 2013

N2 - 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

AB - 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

U2 - 10.1126/science.1240094

DO - 10.1126/science.1240094

M3 - Article

C2 - 23846901

SN - 0036-8075

VL - 341

SP - 186

EP - 191

JO - Science

JF - Science

IS - 6142

ER -