T regulatory Cells in HSV Immunity and Immunopathology

描述（由申请人提供）：单纯疱疹病毒是一种常见的人类病原体，可引起唇疱疹、发热水疱、角膜炎和脑炎。一旦感染，一个人会终身保留病毒，并可能在各种情况下周期性复发疼痛的病变。因此，预防原发性感染或复发性HSV病变是一个重要的公共卫生目标。通过了解HSV感染的基本免疫机制并应用这些策略开发有效的疫苗，这可能会实现。最近，我们观察到在小鼠模型系统中，一类调节性T细胞（Treg）抑制了对HSV感染的保护性免疫。这些细胞还妨碍了某些针对病毒的疫苗配方的功效。然而，同一类型的细胞有利于减少HSV感染引起的免疫病理病变。目前的提案将确定在对HSV感染的初次免疫和回忆免疫期间导致Treg诱导的情况。我们还将尝试确定HSV感染诱导的Treg反应是否会影响对其他超感染的免疫水平。最后，许多不同的策略将被用于调节体内Treg细胞的功能，以增加对HSV的免疫力或减少HSV诱导的免疫病理造成的损伤。

DESCRIPTION (provided by applicant): Herpes simplex virus is a common human pathogen that causes cold sores, fever blisters, keratitis, and encephalitis. Once infected, a person retains the virus life-long and may suffer periodic recurrence of painful lesions that take place under a variety of conditions. Thus, prevention of either primary infections or recurring HSV lesions is an important public health goal. This will likely be achieved by understanding the basic immunity mechanism to HSV infection and applying those strategies to develop effective vaccines. Recently, we observed that in the mouse model system, protective immunity to HSV infection was dampened by a class of regulatory T cells (Treg). Such cells also hampered the efficacy of certain vaccine formulations directed against the virus. However, the same type of cells were beneficial in reducing immunopathological lesions caused by HSV infection. The current proposal will define the circumstances that result in Treg induction during primary and recall immunity to HSV infection. We shall also attempt to determine if the Treg response induced by HSV infection impacts on the level of immunity to other superinfections. Finally, a number of different strategies will be used to modulate the function of Treg cells in vivo to either increase immunity to HSV or reduce the damage resulting from HSV-induced immunopathology.