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Human Cytomegalovirus (HCMV)-infected Astrocytoma Cells Impair the Function of HCMV-specific Cytotoxic T Cells

Journal of Korean Medical Science 2020년 35권 27호 p.218 ~ 218
김지연 ( Kim Ji-Yeon ) - Seoul National University College of Medicine Department of Microbiology and Immunology

이원우 ( Lee Won-Woo ) - Seoul National University College of Medicine Department of Microbiology and Immunology
황응수 ( Hwang Eung-Soo ) - Seoul National University College of Medicine Department of Microbiology and Immunology

Abstract


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.

키워드

Glioblastoma Multiforme; Human Cytomegalovirus; Cytotoxic T Lymphocyte; Astrocytoma Cell; Immediate Early Protein-1
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