Human Cytomegalovirus (HCMV)-infected Astrocytoma Cells Impair the Function of HCMV-specific Cytotoxic T Cells
Jiyeon Kim1,2,3, Won Woo Lee1,2,3, Eung Soo Hwang1,4
1Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea.
Background:
Human cytomegalovirus (HCMV) infection in glioblastoma multiforme (GBM) is associated with a poor prognosis and may affect the pathogenesis of GBM. In this study, we investigated the role of HCMV-infected astrocytoma cells in impairing the activity of cytotoxic T lymphocytes (CTLs) specific to the HCMV protein.
Methods:
CTLs specific to HCMV immediate early (IE)-1 were expanded from peripheral blood mononuclear cells of healthy donors by stimulating CD8+ T lymphocytes with U373MG cells (ATCC HTB-17: male) expressing HCMV IE-1. The death rate of the target and the effector cells was determined by the total count of the remaining respective cells after the interaction of them.
Results:
The death rate of the target cells by CTLs increased depending on HLA restriction and the effector:target (E:T) ratio. The death rate of effector cells in the HCMV-infected U373MG cell culture was 37.1% on day 4 post-infection. The removal of the culture supernatant from HCMV-infected U373MG cells prior to adding the effector cells increased target cell death from 8.4% to 40.8% at E:T = 1:1, but not at E:T = 3:1. The transfer of cells from a 24-hour co-culture of the HCMV-infected U373MG cells and CTLs to HCMV IE-1-expressing target cells resulted in decreasing the cell death rate of the target cells from 31.1% to 13.0% at E:T = 1:1, but not at E:T = 3:1. HCMV infection of U373MG cells decreases the activity of CTLs specific to HCMV when the number of CTLs is low.
Conclusion:
These results suggest that HCMV could impair CTL activity and facilitate glioblastoma growth unchecked by CTLs.
Insights
Human cytomegalovirus (HCMV) infection impairs cytotoxic T lymphocyte (CTL) activity against glioblastoma multiforme (GBM). This HCMV-induced immune suppression may allow GBM tumors to grow unchecked by the immune system.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Human cytomegalovirus (HCMV) infection is linked to poor prognosis in glioblastoma multiforme (GBM) and may influence GBM pathogenesis.
- Investigating HCMV's role in impairing anti-tumor immunity is crucial for understanding GBM progression.
Purpose of the Study:
- To determine how HCMV-infected astrocytoma cells affect the activity of cytotoxic T lymphocytes (CTLs) specific to HCMV proteins.
- To elucidate the mechanism by which HCMV influences the anti-tumor immune response in the context of GBM.
Main Methods:
- Cultured CD8+ T lymphocytes from healthy donors to generate HCMV immediate early (IE)-1 specific CTLs.
- Co-cultured CTLs with HCMV-infected U373MG astrocytoma cells and assessed target cell death and effector cell viability.
- Manipulated culture conditions, including supernatant removal and cell transfer, to evaluate CTL activity.
Main Results:
- HCMV-infected U373MG cells significantly reduced the activity of HCMV-specific CTLs, particularly at lower effector-to-target (E:T) ratios.
- Removal of culture supernatant from infected cells partially restored CTL-mediated target cell killing.
- Co-culture with infected cells and subsequent transfer to new targets demonstrated impaired CTL function.
Conclusions:
- HCMV infection in astrocytoma cells actively suppresses the function of HCMV-specific CTLs.
- This immune suppression by HCMV may contribute to uncontrolled glioblastoma growth by evading T cell-mediated immunity.
More Related Videos
05:53Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
11:15Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
