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，可引起唇疱疹，发热水泡， 角膜炎和脑炎。一旦被感染，一个人会终生保留病毒， 在各种条件下发生的疼痛性损伤的周期性复发。因此，预防 无论是原发性感染或复发性HSV病变是一个重要的公共卫生目标。这将 通过了解HSV感染的基本免疫机制， 这些策略来开发有效的疫苗。最近，我们观察到在小鼠模型中， 系统中，对HSV感染的保护性免疫受到一类调节性T细胞（Treg）的抑制。 这些细胞也阻碍了某些针对病毒的疫苗制剂的效力。 然而，相同类型的细胞在减少由免疫缺陷引起的免疫病理学病变方面是有益的。 HSV感染。目前的建议将定义导致Treg诱导的情况 在对HSV感染的初次免疫和回忆免疫期间。我们还将试图确定Treg HSV感染诱导的免疫应答影响对其他重复感染的免疫水平。 最后，将使用许多不同的策略来调节体内Treg细胞的功能， 增加对HSV的免疫力或减少由HSV诱导的 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.