Mg 2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D

Author:

Chaigne-Delalande Benjamin1,Li Feng-Yen12,O’Connor Geraldine M.3,Lukacs Marshall J.1,Jiang Ping1,Zheng Lixin1,Shatzer Amber4,Biancalana Matthew1,Pittaluga Stefania5,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 Sunil10,Mehmet Huseyin10,Su Helen C.11,Cohen Jeffrey I.3,Uzel Gulbu12,Lenardo Michael J.1

Affiliation:

1. Molecular Development of the Immune System Section, Lymphocyte Molecular Genetics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

2. Biomedical Sciences Graduate Program, University of California–San Francisco, San Francisco, CA 94143, USA.

3. Cancer and Inflammation Program, Laboratory of Experimental Immunology, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

4. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

5. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

6. Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD 20892, USA.

7. Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, OH 45229, USA.

8. Pediatric Hematology, Immunology and Infectious Diseases, Academic Medical Center, Amsterdam, Netherlands.

9. Division of Oncology The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

10. Respiratory and Immunology Division, Merck Research Laboratories, Boston, MA 021159, USA.

11. Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

12. Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Magnesium to the Rescue Individuals with X-linked immunodeficiency with Mg 2+ defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN) disease are genetically deficient for expression of MAGT1 , a magnesium transporter. Chaigne-Delalande et al. (p. 186 ) sought to better understand why these individuals are chronically infected with EBV at high viral loads and are susceptible to the development of lymphomas. CD8 + T cells and natural killer cells, which help to keep EBV infection in check, exhibited reduced cytotoxicity owing to their lower expression of the cell surface receptor NKG2D, which triggers cytolysis upon ligation. Magnesium supplementation in vitro and also in two XMEN patients restored levels of free Mg 2+ , increased NKG2D expression, and resulted in reduced amounts of EBV + cells, suggesting that this may be an effective therapeutic approach for XMEN patients.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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