Kida K, Isozumi R, Ito M
Department of Pediatrics, Mie University School of Medicine, Japan.
Pediatr Int. 2000 Dec;42(6):631-6. doi: 10.1046/j.1442-200x.2000.01315.x.
Human Herpes virus 6 (HHV-6) is a causative agent of exanthema subitum and replicates mainly in lymphocytes. The aim of present study was to investigate cytotoxicity against HHV-6-infected cells by cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC).
Human herpes virus 6-infected and -uninfected lymphocytes were used as target cells. Killing of target cells by CBMC and PBMC was investigated by the chromium release cytotoxicity assay.
Freshly isolated CBMC and PBMC did not lyse HHV-6-infected and -uninfected cells. When CBMC and PBMC were cultured with interleukin (IL)-2, HHV-6-infected cells were significantly lysed compared with uninfected cells. Deletion of CD16+ cells by treatment of effector cells with anti-Leu-11b (CD16) antibody with complement reduced cytotoxicity against HHV-6-infected cells and T lymphocyte-rich cells did not lyse HHV-6-infected cells. Treatment of effector cells with anti-Fas ligand antibody and treatment of HHV-6-infected cells with anti-Fas antibody reduced cytotoxicity against HHV-6-infected cells. DNA fragmentation was detected in the supernatant from HHV-6-infected cells cultured with IL-2-activated lymphocytes. Culture of CBMC and PBMC with IL-12 also enhanced cytotoxicity against HHV-6-infected cells.
These data suggest that lymphocytes cultured with IL-2 or IL-12 mediate killing against HHV-6-infected cells and killing of HHV-6-infected cells was through apoptosis. Fas-Fas ligand interaction is one pathway by which HHV-6-infected cells are killed. Killing of HHV-6-infected cells by NK cells activated by cytokines may play a role in the recovery from HHV-6 infection in vitro.
人疱疹病毒6型（HHV-6）是幼儿急疹的病原体，主要在淋巴细胞中复制。本研究旨在探讨脐血单个核细胞（CBMC）和成人外周血单个核细胞（PBMC）对HHV-6感染细胞的细胞毒性。
将感染和未感染人疱疹病毒6型的淋巴细胞用作靶细胞。通过铬释放细胞毒性试验研究CBMC和PBMC对靶细胞的杀伤作用。
新鲜分离的CBMC和PBMC不会裂解感染和未感染HHV-6的细胞。当CBMC和PBMC与白细胞介素（IL）-2一起培养时，与未感染细胞相比，HHV-6感染的细胞被显著裂解。用抗Leu-11b（CD16）抗体和补体处理效应细胞以去除CD16+细胞，可降低对HHV-6感染细胞的细胞毒性，富含T淋巴细胞的细胞不会裂解HHV-6感染的细胞。用抗Fas配体抗体处理效应细胞和用抗Fas抗体处理HHV-6感染的细胞可降低对HHV-6感染细胞的细胞毒性。在用IL-2激活的淋巴细胞培养的HHV-6感染细胞的上清液中检测到DNA片段化。CBMC和PBMC与IL-12一起培养也增强了对HHV-6感染细胞的细胞毒性。
这些数据表明，用IL-2或IL-12培养的淋巴细胞介导对HHV-6感染细胞的杀伤作用，且对HHV-6感染细胞的杀伤是通过细胞凋亡实现的。Fas-Fas配体相互作用是HHV-6感染细胞被杀伤的一条途径。细胞因子激活的自然杀伤细胞对HHV-6感染细胞的杀伤作用可能在体外HHV-6感染的恢复中起作用。
