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KMID : 0191120200350270218
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Journal of Korean Medical Science
2020 Volume.35 No. 27 p.218 ~ p.218
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Human Cytomegalovirus (HCMV)-infected Astrocytoma Cells Impair the Function of HCMV-specific Cytotoxic T Cells
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Kim Ji-Yeon
Lee Won-Woo
Hwang Eung-Soo
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Abstract
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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.
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KEYWORD
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Glioblastoma Multiforme, Human Cytomegalovirus, Cytotoxic T Lymphocyte, Astrocytoma Cell, Immediate Early Protein-1
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