Regulatory T Cell Activity in Anti-Viral Immunity

抗病毒免疫中的调节性 T 细胞活性

• 批准号: 8089285
• 负责人: ANDREW J CATON
• 金额: $ 27.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089285
• 关键词: Affect; Antibody Formation; Autoimmune Diseases; B-Lymphocytes; Bacteria; Bacterial Infections; CD4 Positive T Lymphocytes; Cells; Development; Exhibits; Goals; Growth; Hemagglutinin; Immune; Immune response; Immune system; Immunity; Immunization; In Vitro; Inbred BALB C Mice; Infection; Infectious Agent; Inflammation; Laboratories; Morbidity - disease rate; Mus; Peptides; Regulatory T-Lymphocyte; Shapes; Site; Specificity; T cell response; T memory cell; T-Cell Antigen Receptor Specificity; T-Cell Receptor; Testing; Tissues; Transgenic Mice; Vaccination; Viral; Virus; Virus Diseases; anti-influenza; base; immunopathology; influenzavirus; mortality; mutant; pathogen; prevent; response; thymocyte

There is strong evidence that CD4+CD25+Foxp3+ regulatory T (Treg) cells are generated intrathymically in response to self-peptides. Yet, Treg cells also modify immune responses to infectious agents, and how selfpeptide- specific Treg cells can recognize and modify anti-pathogen immune responses, including B and T cell memory formation, is currently unknown. In preliminary studies we have found that Treg cells that are generated based on their specificity for the influenza virus hemagglutinin when it is expressed as a selfantigen in transgenic mice can modulate immune responses to influenza virus. This project will test the hypothesis that Treg cells that have been generated based on specificity for self-peptides can modulate immune responses to influenza virus following activation by crossreactive viral peptides, by bacterial peptides, or by self-peptides at the site of infection. Aim 1 will determine how such Treg cell activity impacts anti-influenza virus immunity. The ability of Treg cells to modulate the development of protective antibody responses following influenza virus vaccination, and how their activity can affect virus clearance, anti-viral immunity and the inflammation and tissue damage that are induced by influenza virus infection will be assessed. Aim 2 will determine how infection can modify the representation and activity of Treg cells. Whether influenza virus infection induces short- or long-term changes in the Treg cell repertoire, and the extent to which Treg cell activation in response to influenza virus infection can alter the immune response to a concurrent or subsequent bacterial infection (or vice versa) will be examined. Aim 3 will determine how TCR specificity for viral and/or self-peptides can guide Treg cell activity in infected hosts. Whether activation of self-peptide-specific Treg cells by weakly crossreactive viral peptides can modify the immune response to influenza virus infection will be examined, and the ability of self-peptides to activate Treg cells to modify the immune response to influenza virus infection will be assessed. The long-term goal is to determine whether and how Treg cell activity might be modified to enhance vaccination and/or limit the morbidity and mortality caused by influenza virus infection.

有强有力的证据表明，CD 4 + CD 25 + Foxp 3+调节性T（Treg）细胞在胸腺内产生， 对自身肽的反应。然而，Treg细胞也改变了对感染因子的免疫反应，以及自身肽- 特异性Treg细胞可以识别和修饰抗病原体免疫应答，包括B和T 细胞记忆的形成，目前尚不清楚。在初步研究中，我们发现， 当流感病毒血凝素表达为自身抗原时， 可以调节对流感病毒的免疫反应。该项目将测试 假设已经基于对自身肽的特异性产生的Treg细胞可以调节 在被交叉反应性病毒肽、细菌肽和细菌肽激活后对流感病毒的免疫应答 肽，或通过感染部位的自身肽。目标1将确定这种Treg细胞活性如何影响 抗流感病毒的免疫力。Treg细胞调节保护性抗体产生的能力 流感病毒疫苗接种后的反应，以及它们的活性如何影响病毒清除，抗病毒 流感病毒感染引起的免疫力、炎症和组织损伤， 评估。目的2将确定感染如何改变Treg细胞的表达和活性。 流感病毒感染是否诱导Treg细胞库的短期或长期变化，以及 响应于流感病毒感染的Treg细胞活化可以改变免疫应答的程度， 将检查并发或随后的细菌感染（或反之亦然）。目标3将决定如何 TCR对病毒和/或自身肽的特异性可以指导受感染宿主中的Treg细胞活性。活化是否 自身肽特异性Treg细胞的弱交叉反应性病毒肽可以改变免疫应答， 将检查流感病毒感染，并检查自身肽激活Treg细胞以修饰细胞的能力。 将评估对流感病毒感染的免疫应答。长期目标是确定 以及如何修饰Treg细胞活性以增强疫苗接种和/或限制发病率和死亡率 由流感病毒感染引起。