T CELL RESPONSES DURING ACUTE VIRAL ENCEPHALITIS

急性辛德毕斯病毒（SV）感染的炎症反应， 中枢神经系统（CNS）已经在鼠模型中表征。 这种疾病是虫媒病毒性脑炎的代表， 作为研究CNS内免疫反应的模型。脑脊液 SV脑炎期间的炎症，在早期达到高峰， 感染，由T细胞和自然杀伤细胞组成。实质 炎症最大后，并出现更复杂的细胞 混合物.病毒随后从CNS中清除，并且小鼠 感染野生型的病人都能顺利康复的首要目标 拟议的实验是为了表征中枢神经系统的发展， SV脑炎期间的T细胞反应在整个治疗过程中 感染具体的调查将集中在详细的表型 研究浸润CNS的T细胞，以及表征 其功能特性。这些也包括细胞因子的产生 如抗病毒增殖和细胞毒性反应。其他 实验将研究初步发现的意义 这些研究表明，γ δ + T细胞优先聚集在 在CNS内，尤其是在感染早期。由于具体 T细胞与脑毛细血管内皮细胞的分子相互作用 细胞可能调节淋巴细胞外渗进入CNS， 血管周围炎症的发展，本提案的进一步目标 将探索这两种细胞之间粘附事件的本质 急性脑炎期间的人群。这将使用以下两种方法执行： 淋巴细胞和组织切片之间的体外细胞粘附测定 感染动物的脑实质，以及体内 T细胞归巢进入CNS的测定。单克隆抗体阻断实验 计划抗体以确定相关分子 T细胞和CNS微血管内皮细胞之间的相互作用， 体外和体内。体外测定也可用于筛选和鉴定 鉴定目前未表征的受体-配体相互作用， 在这种情况下进行调解。探索T细胞的这些特征将 不仅对理解急性病毒性心肌炎的发病机制很重要， 脑炎，但也有其他炎性条件的中枢神经系统， 推测是T细胞介导的。

The inflammatory response to acute Sindbis virus (SV) infection of the central nervous system (CNS) has been characterized in a murine model. This disease is representative of arboviral encephalitis, and it serves as a model to study immune reactions within the CNS. Cerebrospinal fluid inflammation during SV encephalitis, which reaches a peak early in infection, is composed of T cells and natural killer cells. Parenchymal inflammation is maximal later, and appears more complex in cellular composition. The virus is subsequently cleared from the CNS, and mice with the wild-type infection recover uneventfully. The primary goal of the proposed experiments is to characterize the development of the CNS T cell response during SV encephalitis over the full course of the infection. Specific investigations will focus on detailed phenotypic study of T cells that infiltrate the CNS, as well as characterization of their functional properties. These include cytokine production as well as anti-viral proliferative and cytotoxic responsiveness. Other experiments will investigate the significance of preliminary findings which have shown that gamma delta plus T cells accumulate preferentially within the CNS, especially early in infection. Since the specific molecular interactions between T cells and cerebral capillary endothelial cells likely regulate lymphocyte extravasation into the CNS and the development of perivascular inflammation, further goals of this proposal will be to explore the nature of adhesion events between these two cell populations during acute encephalitis. This will be performed using both an in vitro cell adhesion assay between lymphocytes and tissue sections of brain parenchyma from infected animals, as well as with an in vivo assay of T cell homing into the CNS. Blocking experiments with monoclonal antibodies are planned in order to determine the relevant molecular interactions between T cells and CNS microvascular endothelium both in vitro and in vivo. The in vitro assay may also serve to screen for and identify presently uncharacterized receptor-ligand interactions that mediate binding in this setting. Exploring these features of T cells will be important for understanding not only the pathogenesis of acute viral encephalitis, but also other inflammatory conditions of the CNS which are presumed to be T cell-mediated.