T regulatory Cells in HSV Immunity and Immunopathology

单纯疱疹病毒是一种常见的人类病原体，会引起口疮、发烧、水泡、 角膜炎和脑炎。一旦被感染，人就会终身感染该病毒，并可能遭受 痛性皮损在各种情况下发生的周期性复发。因此，预防 预防原发感染或复发单纯疱疹病毒感染是一个重要的公共卫生目标。这将是 可能是通过了解HSV感染的基本免疫机制和应用 这些策略有助于开发有效的疫苗。最近，我们观察到在小鼠模型中 系统中，对HSV感染的保护性免疫被一类调节性T细胞(Treg)抑制。 这些细胞还阻碍了针对该病毒的某些疫苗配方的效力。 然而，相同类型的细胞在减少由以下原因引起的免疫病理损害方面是有益的 单纯疱疹病毒感染。目前的提案将定义导致Treg诱导的条件 在初选期间和召回期间对HSV感染具有免疫力。我们还将尝试确定Treg是否 单纯疱疹病毒感染引起的免疫应答影响机体对其他重叠感染的免疫水平。 最后，将使用一些不同的策略来调节体内Treg细胞的功能，以 要么提高对HSV的免疫力，要么减少HSV诱导的损害 免疫病理学。

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 circumstancesthat 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.