사람세포거대바이러스에 감염된 뇌신경종양세포에 의한 IE-1특이 세포독성 T림프구의 기능 감소

Abstract

Background Glioblastoma multiforme (GBM) is a rapid growing and invading tumor of glial origin with a poor prognosis. The level of human cytomegalovirus (HCMV) infection in GBM correlates with a prognosis and HCMV may involve the pathogenesis of GMB. Here I sought to verify a role of HCMV-infected astrocytoma cells on impairing the activity of cytotoxic T lymphocytes (CTLs) specific to HCMV immediate early (IE)-1. Methods CTLs specific to HCMV IE-1 were prepared by the stimulation of the purified CD8+ cells from donors with U373MG expressing HCMV IE-1. Death rate of the target cells was determined by the total counting of the remaining target cells after ii the interaction of the effector and the fluorescent dye-tagged target cells. Death rate of the effector cells was assayed by Annexi n V or TUNEL staining. Results Cell death rate of the target cells by CTLs increased HLA-restrictedly and depending on effector:target(E:T) ratio. The death rate of effector cells in the culture of HCMV-infected U373MG were 37.1% at day 4 postinfection, and 4.5x104 PFUs/ml were detected at that time. Removal of the culture supernatant from HCMV-infected U373MG at day 4 postinfection before adding effector cells enhanced the target death from 12.3% to 39.1% at E:T=1:1, but not at E:T=3:1. When the effector cells from 24-hour co-cultured HCMV-infected U373MG with CTLs were transferred to U373MG expressing HCMV IE-1 and cultured for another 24 hours, cell death rate of the target cells decreased from 31.5% to 14.3% at E:T=1:1, but increased from 41.5% to 65.3% at E:T=3:1. Conclusion Productively infected U373MG with HCMV decreases the activity of CTLs specific to HCMV in case of the low number of the effector cells. These results suggest that HCMV could impair CTL activity and help glioblastoma unchecked by CTLs.