登革病毒抗体依赖增强感染是重症登革热疾病主要风险因素之一。研究显示，亚中和/非中和滴度抗体调理吞噬介导的病毒感染能够抑制细胞固有免疫途径从而促进病毒增殖。我们前期研究表明，抗体依赖增强感染单核细胞能够特异上调细胞自噬途径，进而抑制RIG-I/MDA-5介导的抗病毒固有免疫。然而免疫健全小鼠抗体依赖增强感染模型显示，抑制自噬的病理保护作用并不取决于降低的病毒血症。结合自噬在外源性抗原提呈中的潜在作用，我们推测靶细胞中增强的自噬反应亦可能通过调节适应性免疫反应促进重症登革病理发生。本研究中，我们拟整合分析DENV-ADE动物模型中自噬对T细胞功能和谱系分化，CD4+ /CD8+ T细胞免疫谱系组成和免疫显性表位的转变的影响，从适应性免疫角度深入探讨自噬在重症登革病理发生中的作用机制。本研究将有助于加深对重症登革病理机制理解，为疾病防治提供潜在靶点。

Antibody dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe Dengue diseases. Through opsonization by subneutralizing or non-neutralizing antibodies, DENV infection suppresses innate cell immunity to facilitate viral replication. Our previous study demonstrated that DENV-ADE infection of monocytes could induce autophagy formation，the early induced autophagic proteins ATG5-ATG12 participate in suppression of RLR-MAVS signalling axis. However, the protective role autophagy inhibitor in DENV-ADE model did not readily rely on suppression of virus production. In consideration of the potential role of autophagy in MHC depended.antigen presentation, it would be reasonable to postulate that the induction of autophagy in DENV-ADE infected monocytes may participate in the pathogenesis of severe dengue disease. In this study, we will Integrated analysis the autophagic effects on lineage differentiation and immune repertoire of CD4+ T/CD8+ T subsets in the ADE condition. Further investigation of the role of autophagy in severe dengue disease will help to add knowledge about the complexity of ADE infection and contribute further to research on therapeutic strategies.