探討不同劑量的流感病毒感染以及施打疫苗對調節性T細胞生成的影響

The effects of the viral dose and immunization on induction of influenza virus antigen-specific regulatory T cells

黄詠妍(Weng-In Wong)

指導教授 ： 楊宏志

國立臺灣大學/醫學院/微生物學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.01853

摘要

現時的流感疫苗主要是針對B細胞免疫來進行設計，使宿主產生強而有效的中和性抗體以阻止病毒的入侵。由於流行性感冒病毒的表面抗原具有高度變異性，導致流感疫苗需每年重新施打，相對地，可辨認具有高度一致性的病毒內部蛋白質的T細胞免疫將會成為新一代流感疫苗設計的思考方向。因此，我們實驗室主要針對探討哪些因子影響對抗流感病毒的T細胞免疫，希望能藉此設計出有效的T細胞疫苗。而最近的研究證明在急性流感病毒感染中會產生具有流感病毒特異性的調節性T細胞，但這些具有抗原特異性的調節性T細胞在急性流感病毒感染時所參與的免疫作用以及角色到目前還不明確。我們在這篇論文裹利用一株帶有卵白蛋白 (Ovalbumin, OVA) 抗原決定部位的A型流感病毒，PR8-OVAII，作為感染模式，去研究具有抗原特異性的調節性T細胞在免疫作用時以及感染不同劑量的流感病毒中的角色是如何。根據我們的研究結果顯示，感染低劑量的病毒比感染高劑量的流感病毒產生較多的抗原特異性的調節性T細胞，而施打疫苗，同樣是一個較弱的免疫刺激，亦會促進具有抗原特異性的調節性T細胞的產生。因此我們認為，在一個較弱的免疫刺激之下較容易產生抗原特異性的調節性T細胞，這些產生出來的具有抗原特異性的調節性T細胞對後續對抗流感病毒的免疫反應會造成什麼影響是我們下一步想要去探討的。

關鍵字

調節性T細胞 ； 流感病毒 ； 疫苗 ； 不同病毒劑量

並列摘要

Current influenza vaccine mainly focuses on inducing a strong B cell immunity based on neutralizing antibody to prevent the influenza virus infection. Due to the high mutation rate of influenza surface antigens, annual vaccination is necessary. T cell immunity targeting the conserved internal proteins is thus a candidate for designing a new type of influenza vaccine against a broad spectrum of viral strains. Therefore, we are interested in the factors that which affect T cell immunity against influenza virus. Recent studies have demonstrated that influenza virus-specific regulatory T (Treg) cells can be induced during acute influenza virus infection, but little is known about the role of Treg cells in regulating the immune response during acute influenza virus infection. Here, using OVA epitope-containing influenza A virus (PR8) as a model, we studied the role of viral antigen-specific Treg cells during immunization and different doses of influenza virus infection. We found that, low-dose infection promoted the induction of viral antigen-specific Treg cells. In addition, immunization, another suboptimal immune stimulation, also induced antigen-specific Treg cells. Understanding how these viral antigen-specific Treg cells affect T cell immunity will help us design better vaccine strategy against the infection of highly mutated and emerging pandemic strains of influenza virus.

並列關鍵字

Regulatory T cells ； influenza virus ； vaccine ； viral dose

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