Chachu Karen A, LoBue Anna D, Strong David W, Baric Ralph S, Virgin Herbert W
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
PLoS Pathog. 2008 Dec;4(12):e1000236. doi: 10.1371/journal.ppat.1000236. Epub 2008 Dec 12.
Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure. For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated. We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes. Further, long-lasting protective immunity was generated by oral live virus vaccination. Systemic vaccination with the MNV capsid protein also effectively protected against mucosal challenge, while vaccination with the capsid protein of the distantly related human Lordsdale virus provided partial protection. Fully effective vaccination required a broad immune response including CD4 T cells, CD8 T cells, and B cells, but the importance of specific immune cell types varied between the intestine and intestinal lymph nodes. Perforin, but not interferon gamma, was required for clearance of MNV infection by adoptively transferred T lymphocytes from vaccinated hosts. These studies prove the feasibility of both mucosal and systemic vaccination against mucosal norovirus infection, demonstrate tissue specificity of norovirus immune cells, and indicate that efficient vaccination strategies should induce potent CD4 and CD8 T cell responses.
病毒免疫的两个主要表现是有效清除急性感染以及针对二次病毒暴露进行疫苗接种的能力。对于诺如病毒，T细胞对病毒清除和疫苗接种的作用尚未阐明。我们在此报告，CD4和CD8 T细胞都是从小肠和肠淋巴结中有效清除原发性小鼠诺如病毒（MNV）感染所必需的。此外，口服活病毒疫苗可产生持久的保护性免疫。用MNV衣壳蛋白进行全身疫苗接种也能有效抵御黏膜攻击，而用远缘相关的人类洛兹代尔病毒的衣壳蛋白进行疫苗接种则提供部分保护。完全有效的疫苗接种需要包括CD4 T细胞、CD8 T细胞和B细胞在内的广泛免疫反应，但特定免疫细胞类型的重要性在小肠和肠淋巴结之间有所不同。过继转移自接种宿主的T淋巴细胞清除MNV感染需要穿孔素，而不是干扰素γ。这些研究证明了针对黏膜诺如病毒感染进行黏膜和全身疫苗接种的可行性，证明了诺如病毒免疫细胞的组织特异性，并表明有效的疫苗接种策略应诱导强大的CD4和CD8 T细胞反应。
