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ResearchIn-Press PreviewImmunologyTransplantation
Open Access | 10.1172/JCI179561
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Mülling, N. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Behr, F. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Heieis, G. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Boss, K. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by van Duikeren, S. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by van Haften, F. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Pardieck, I. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by van der Gracht, E. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Vleeshouwers, W. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by van der Sluis, T. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by de Graaf, J. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Veerkamp, D. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Franken, K. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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Lei, X.
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1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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van de Sand, L.
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1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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van der Burg, S.
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1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Welters, M. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Heidt, S. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Huisman, W. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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Jochems, S.
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1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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Giera, M.
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1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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de Vries, A.
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1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Kribben, A. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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Everts, B.
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1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Wilde, B. in: JCI | PubMed | Google Scholar
1Immunology, Leiden University Medical Center, Leiden, Netherlands
2Parasitology, Leiden University Medical Center, Leiden, Netherlands
3Nephrology, University Hospital Essen, Essen, Germany
4Infectious Diseases, University Hospital Essen, Essen, Germany
5Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
6Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands
7Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
Find articles by Arens, R. in: JCI | PubMed | Google Scholar
Published July 2, 2024 - More info
Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in immunocompromised individuals such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in immunosuppressed individuals have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in immunocompromised patients and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with non-controlled CMV infection. These dysregulations comprise impaired glycolysis and increased mitochondrial stress, which is associated with an intensified expression of the nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity of CD38 reinvigorated the metabolism and improved cytokine production of CMV-specific CD8+ T cells. These findings were corroborated in a mouse model of CMV infection under conditions of immunosuppression. Thus, dysregulated metabolic states of CD8+ T cells could be targeted by inhibiting CD38 to reverse hypo-responsiveness in individuals who fail to control chronic viral infection.