Back to Search
Start Over
Inhibiting the NADase CD38 improves cytomegalovirus-specific CD8+ T cell functionality and metabolism.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2024 Jul 02; Vol. 134 (17). Date of Electronic Publication: 2024 Jul 02. - Publication Year :
- 2024
-
Abstract
- Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in people who are immunocompromised, such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in people who are immunosuppressed have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in patients who are immunocompromised and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with noncontrolled 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 hyporesponsiveness in individuals who fail to control chronic viral infection.
- Subjects :
- Animals
Humans
Mice
Male
Membrane Glycoproteins immunology
Membrane Glycoproteins genetics
Membrane Glycoproteins metabolism
Female
Kidney Transplantation
Middle Aged
Immunocompromised Host immunology
Adult
Glycolysis
ADP-ribosyl Cyclase 1 immunology
ADP-ribosyl Cyclase 1 metabolism
ADP-ribosyl Cyclase 1 genetics
Cytomegalovirus Infections immunology
CD8-Positive T-Lymphocytes immunology
Cytomegalovirus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 134
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 38954588
- Full Text :
- https://doi.org/10.1172/JCI179561