Song W, Collisson E W, Li J, Wolf A M, Elder J H, Grant C K, Brown W C
Department of Veterinary Pathobiology, Texas A&M University, College Station, USA.
Virology. 1995 Jun 1;209(2):390-9. doi: 10.1006/viro.1995.1271.
We have previously reported the presence of feline immunodeficiency virus (FIV)-specific, major histocompatibility complex (MHC)-restricted cytolytic T lymphocytes (CTL) in experimentally FIV-infected cats. However, the fine specificity of the CTL and the role of individual FIV proteins in inducing FIV-specific CTL responses remain unknown. In this study, we examined the in vitro induction and activity of FIV p24 capsid-specific CTL obtained from cats that had been experimentally infected with FIV Petaluma for 30 to 56 months. An amphotropic murine retroviral vector was used to generate transgenic primary feline T lymphoblasts that expressed the FIV capsid protein. When the autologous capsid-transduced T cells were used in vitro to stimulate CTL responses from peripheral blood mononuclear cells of chronically infected cats, MHC-restricted lysis of virus-infected target cells was observed. The majority of the CTL expressed CD8, and depletion of this population, but not CD4+ cells, effectively diminished the CTL activity. When the autologous capsid-transduced T cells were used as target cells, lysis by capsid-induced effectors was not observed. Analysis of capsid-transduced T cell clones revealed a variable and low level of capsid expression among the clones. This study demonstrates the potential for using retroviral vectors as a means of inducing CTL effector cells that will specifically kill lentivirus-infected cells during lentiviral infection.
我们之前曾报道,在实验性感染猫免疫缺陷病毒(FIV)的猫中存在FIV特异性、主要组织相容性复合体(MHC)限制性细胞毒性T淋巴细胞(CTL)。然而,CTL的精细特异性以及单个FIV蛋白在诱导FIV特异性CTL反应中的作用仍不清楚。在本研究中,我们检测了从实验性感染FIV佩塔卢马株30至56个月的猫中获得的FIV p24衣壳特异性CTL的体外诱导和活性。使用一种嗜性鼠逆转录病毒载体来产生表达FIV衣壳蛋白的转基因原代猫T淋巴母细胞。当在体外使用自体衣壳转导的T细胞刺激慢性感染猫外周血单个核细胞的CTL反应时,观察到病毒感染靶细胞的MHC限制性裂解。大多数CTL表达CD8,去除该群体而非CD4 +细胞可有效降低CTL活性。当使用自体衣壳转导的T细胞作为靶细胞时,未观察到衣壳诱导的效应细胞的裂解作用。对衣壳转导的T细胞克隆的分析显示,各克隆中衣壳表达水平可变且较低。本研究证明了使用逆转录病毒载体作为诱导CTL效应细胞的一种手段的潜力,这些效应细胞将在慢病毒感染期间特异性杀伤慢病毒感染的细胞。