权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Cytotoxic Lymphocytes and HSV-1 Corneal Lesions

细胞毒性淋巴细胞和 HSV-1 角膜病变

基本信息

批准号：
7341604
负责人：
ROBERT L HENDRICKS
金额：
$ 34.1万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-09-30 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7341604
关键词：
Adoptive Transfer Afferent Neurons Antibodies Antigens Binding Biological Assay Bromodeoxyuridine CD8-Positive T-Lymphocytes CD8B1 gene CXCL10 gene Candidate Disease Gene Cell Survival Cells Chemotactic Factors Confocal Microscopy Cornea Corneal Diseases Cytoplasmic Granules Cytoprotection Defensins Epitopes Exocytosis Flow Cytometry Fluorescence Funding Gene Expression Genes Glycoproteins Herpesvirus 1 Homeostasis Image Immune system Immunity Immunodominant Epitopes Infiltration Interferon Type II Interferons Interleukin-15 Knockout Mice Label Lesion Life Lymphocyte Lytic MHC Class I Genes Maintenance Measures Mediating Mediator of activation protein Memory Morbidity - disease rate Mouse Strains Mus Neurons Numbers Peptides Physiologic pulse Principal Investigator Process Production Proteins Psychological reinforcement Pulse taking RANTES Reaction Recombinants Recurrence Role Staging Staining method Stains Structure of trigeminal ganglion Synapses T memory cell T-Lymphocyte Testing Time Tumor Necrosis Factor-alpha Tumor Necrosis Factors Viral Viral Gene Expression Regulation Virus Visual chemokine chemokine receptor cytokine cytotoxic cytotoxicity day density fluorescence imaging human TNF protein in vivo killings latent infection neuron apoptosis perforin peripheral blood prevent programs promoter reactivation from latency recombinant virus

项目摘要

DESCRIPTION (provided by applicant): Recurrent herpes simplex virus type 1 (HSV-1) corneal disease, a leading cause of visual morbidity worldwide, results from reactivation of virus that is in a latent (quiescent) state in sensory neurons. During the past funding period we demonstrated that CD8+ T lymphocytes are selectively attracted to the ophthalmic branch of the trigeminal ganglion (TG), appear to form synaptic junctions with neurons, and become activated after the virus has established a latent infection. These findings refute the view that HSV-1 is invisible to the immune system during latency. Moreover, the HSV-1 specific CD8+ T cells were found to inhibit HSV-1 reactivation from latency in neurons, in part through the production of IFN-. In the next period we propose to use real-time fluorescence, and confocal imaging of whole TG and TG cultures, genetically modified mouse strains, and recombinant HSV-1 that express fluorescent proteins from a variety of viral promoters to directly explore the molecular interactions that maintain a pool of HSV-1 specific memory CD8+ T cells in the latently infected TG, and mediate their regulation of viral gene expression in neurons. In Specific Aim 1 we will identify the mechanisms by which CD8+ T cells can block HSV-1 reactivation from latency; in Specific Aim 2 we will identify factors that regulate differential expression of the functional program of CD8+ T cells in blocking HSV-1 reactivation from latency; and in Specific Aim 3 we will explore the factors that contribute to the maintenance of a pool of HSV-1 specific memory CD8+ T cells in the latently infected TG.

描述（由申请人提供）：复发性单纯疱疹病毒1型（HSV-1）角膜疾病是世界范围内视觉疾病的主要原因，是由感觉神经元中处于潜伏（静止）状态的病毒重新激活引起的。在过去的资助期间，我们证明CD8+ T淋巴细胞被选择性地吸引到三叉神经节（TG）的眼部分支，似乎与神经元形成突触连接，并在病毒建立潜伏感染后被激活。这些发现驳斥了HSV-1在潜伏期对免疫系统不可见的观点。此外，发现HSV-1特异性CD8+ T细胞在神经元潜伏期抑制HSV-1再激活，部分是通过产生IFN-。在接下来的一段时间里，我们建议使用实时荧光和共聚焦成像全TG和TG培养物，转基因小鼠菌株和表达各种病毒启动子荧光蛋白的重组HSV-1，直接探索在潜伏感染的TG中维持HSV-1特异性记忆CD8+ T细胞池的分子相互作用，并介导它们对神经元中病毒基因表达的调节。在特异性目标1中，我们将确定CD8+ T细胞阻断HSV-1潜伏性再激活的机制；在特异性目标2中，我们将确定调节CD8+ T细胞功能程序差异表达的因子，以阻止HSV-1从潜伏期再激活；在特异性目的3中，我们将探讨在潜伏感染的TG中维持HSV-1特异性记忆CD8+ T细胞池的因素。