探討抗原特異性調節性T細胞在急性流感中的特性

Abstract

流行性感冒病毒的表面抗原具有高度變異性，因此每年必須重新施打流感疫苗以產生能抵抗病毒入侵的抗體，如何建立針對內部高度一致性病毒內部蛋白質攻擊的T細胞免疫成為流感疫苗發展的方向之一。近日，在動物模式及流行病學上的觀察顯示施打季節性流感疫苗可能對於流行性流感的感染有害，由於調節性T細胞已被認為在其他疾病的疫苗中會使產生的免疫力減弱；另一方面，最近的研究證實了感染流感病毒存在著一群抗原特異性的調節性T細胞，我們實驗室於是想要釐清施打疫苗引發出的抗原特異性調節性T細胞在急性流感中扮演的角色。 在這個研究中，我們利用帶有卵白蛋白抗原決定部位的A型流感病毒PR8-OVAII和OT-II老鼠建立動物模式來研究疫苗引發出的抗原特異性調節性T細胞之特性。研究結果顯示，在第二次感染流感時，由疫苗引發出的抗原特異性調節性T細胞會隨著感染的劑量增加而增加；並且，在局部發炎的部分抗原特異性調節性T細胞傾向於抑制抗原特異性的CD8+ T細胞，抗原特異性調節性T細胞在局部比非專一的調節性T細胞有更強的抑制能力。

People are recommended to get vaccinated annually to induce the antibody against influenza virus because the high variation of surface proteins on influenza virus. Therefore, to establish robust T cell immunity targeting the conserved internal proteins has been one of potential strategies to develop vaccines against heterosubtypic IAV. Recently, observations on the animal model and epidemiology indicated that vaccination against seasonal influenza may interfere with the development of immunity against other subtypes. As regulatory T cells (Tregs) have been shown to suppress protective immune responses to vaccines; in addition, recent studies demonstrated the existence of antigen-specific Tregs during acute influenza virus infection. We thus decide to elucidate the role of vaccination-induced Tregs during acute influenza virus infection. In this study, we established a system by using class II MHC-restricted OVA epitope-containing influenza A virus (PR8-OVAII) to characterize the role of vaccination-induced Tregs. We found that vaccination-induced Tregs accumulated in the lung and draining lymph node upon IAV infection in a dose-dependent manner. Additionally, vaccination-induced Tregs tend to suppress viral antigen-specific CD8+ cells in the local inflammation site during IAV infection. Antigen-specific Tregs exhibit higher suppressive ability than non-specific Tregs do.