A mouse model to study immunity against pseudorabies virus infection:: significance of CD4+ and CD8+ cells in protective immunity
A mouse model to study immunity against pseudorabies virus infection:: significance of CD4+ and CD8+ cells in protective immunity
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DOI：
10.1016/s0264-410x(98)00044-9
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发表时间：
1998-10-01
期刊：
影响因子：
5.5
通讯作者：
Kimman, TG
中科院分区：
文献类型：
--
作者：
Bianchi, ATJ;Moonen-Leusen, HWM;Kimman, TG
本研究首先建立了伪狂犬病病毒免疫/攻毒模型，研究了伪狂犬病病毒感染小鼠的情况。用小鼠模型研究了CD 4（+）和CD 8（+）细胞以及IFN γ产生在保护性免疫中的意义。通过在接种之前和接种时腹膜内注射藻酸盐包封的产生抗-CD 4、-CD 8或-IFN γ的杂交瘤，在体内获得CD 4（+）和CD 8（+）和IFN γ的功能性耗竭。观察到的保护性免疫与潜在的免疫反应，如PRV特异性DTH反应，淋巴细胞增殖和细胞毒性。还通过相同的体内耗竭技术研究了CD 4（+）和CD 8（+）细胞以及IFN γ产生对这些免疫应答的意义。结果表明，小鼠的保护性疫苗接种可以通过用10（7）空斑形成单位的无毒力PRV突变体NIA 3 TK-免疫诱导，其特征在于典型的抗病毒Th 1型免疫应答。一个明确的PRV特异性，CD 4依赖性DTH反应和经典的CD 8依赖性，MHC限制性细胞毒性诱导后，保护性免疫和体液免疫反应有一个偏向PRV特异性IgG 2a的形成。在体内治疗与抗-CD 8和抗-IFN γ表明，细胞毒性反应和体液IgG 2a反应，分别强烈减少，而对致命的挑战保护不受影响。另一方面，抗CD 4处理降低了诱导的保护，使得30%的小鼠在致死攻击后死亡。本研究结果表明，CD 4（+）、DTH样效应细胞是PRV保护性免疫的重要效应机制。(C)1998爱思唯尔科技有限公司版权所有。
In this study we firstly established a vaccination/challenge model to study pseudorabies virus infection in mice. The mouse model was used to investigate the significance of CD4(+) and CD8(+) cells and of IFN gamma production in protective immunity. Functional depletion of CD4(+) and CD8(+) and IFN gamma was obtained in vivo by intraperitoneal injection of alginate-encapsulated anti-CD4, -CD8 or -IFN gamma producing hybridoma's before and at the moment of vaccination. The observed protective immunity was correlated with underlying immunologic responses such as PRV-specific DTH reactivity lymphoproliferation and cytotoxicity. The significance of CD4(+) and CD8(+) cells and of IFN gamma production was also investigated for these immunological responses by the same in vivo depletion technique. The results demonstrated that protective vaccination of mice, that could be induced by immunization with 10(7) plaque forming units of the avirulent PRV mutant NIA3 TK-, was characterized by a typical anti-viral Th1 type immune response. A clear PRV-specific, CD4-dependent DTH reactivity and a classical CD8-dependent, MHC-restricted cytotoxicity was induced after protective immunization and the humoral immune response had a bias towards PRV-specific IgG2a formation. In vivo treatment with anti-CD8 and anti-IFN gamma demonstrated that the cytotoxic response and humoral IgG2a response, respectively, were strongly reduced, whereas protection against lethal challenge was unaffected. On the other hand anti-CD4 treatment reduced the induced protection so that 30% of the mice died after lethal challenge. The results of our study demonstrated that CD4(+), DTH like effector cells are a crucial effector mechanism for protective immunity against PRV. (C) 1998 Elsevier Science Ltd. All rights reserved.