通过接种达到免疫保护和免疫病理的平衡是安全有效疫苗的关键。呼吸道合胞病毒（RSV）是呼吸道感染常见和重要的病原，也是发生哮喘、喘息和并发感染的主要诱因。由于对RSV诱导免疫保护机制不清，早期福尔马林灭活疫苗（FI－RSV）加重了自然感染病理，给新疫苗研发带来了巨大阴影和挑战。我们前期研究提示，初次RSV病毒感染或抗原接种后，总体和RSV特异的调节性CD4 T淋巴细胞（Treg）数量下降。应对再次刺激，Treg的反应程度减弱，对免疫效应细胞的调节作用下降。虽然Treg功能失衡被认为是FI-RSV加重自然感染病理的要因之一，但RSV对Treg反应动力学的影响和机理不清。本项目拟进一步从细胞的分化和免疫记忆来探讨RSV对Treg的影响，以及再次应答时Treg反应减弱的机制。其结果对了解RSV病理机制，对选择性地诱导免疫应答而达到有效的免疫保护和减少免疫病理有指导意义，为安全疫苗设计建立理论基础。

Balanced immunity and immunopathogenesis is the key of safe and effective vaccination. Respiratory syncytial virus (RSV) is one of the most common and important viral pathogens of respiratory tract infection, and associated with asthma, wheeze and other bacterial and fungal infections. Although the importance of RSV as a respiratory pathogen has been recognized for over 50 years, a vaccine is not yet available because of several problems inherent in RSV vaccine development. Early vaccine trial with formalin-inactivated RSV (FI-RSV) in 60s failed with enhanced disease and two fatal cases, which generated a great hurdle and challenge to new vaccine development. Our previous observation suggested that regulatory CD4 T cell (Treg) counts and function declined after primary RSV antigen encounter. In response to secondary challenge, bulk- and RSV specific-Tregs mounted a diminished response with poor suppression on effective T cells. Diminished Treg response has been associated with the enhanced illness of FI-RSV. In this study, we are going to explore kinetics of Treg response to primary and secondary infections, and how RSV infection alters Treg response, and the cellular source of secondary Treg response. Our study will have an insight into RSV pathogenesis, provide a clue of how RSV infection altering the balance of immunity and immunopathogenesis, and benefit new vaccine development.