Role of Chemokines on C8+ Tau cell Effector Functions during MCMV infection

MCMV 感染过程中趋化因子对 C8 Tau 细胞效应功能的作用

• 批准号: 7679296
• 负责人: Tania Nevers
• 金额: $ 2.85万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7679296
• 关键词: Acute; Affect; Antigen-Presenting Cells; Antiviral Agents; Biologic Characteristic; Biological Assay; Biology; CD8-Positive T-Lymphocytes; CD8B1 gene; CXCL10 gene; CXCL9 gene; CXCR3 gene; Cells; Chemotaxis; Complex; Cytomegalovirus Infections; Effector Cell; Event; Family; Flow Cytometry; Generations; Glycoproteins; Herpesviridae; Immune; Immune response; Immune system; Immunity; Infection; Interferons; Leukocytes; Ligands; Liver; Lymphocyte; Lymphocyte Activation; Measures; Mediating; Modeling; Monokines; Mouse cytomegalovirus 1 MCK-2 protein; Murid herpesvirus 1; Play; Production; Proteins; Recruitment Activity; Role; Satellite Viruses; Shapes; Site; Source; Surface; T-Cell Proliferation; T-Lymphocyte; TNF gene; Tissues; Upper arm; Viral; Virus; Virus Diseases; cell type; chemokine; chemokine receptor; cytokine; cytotoxicity; in vivo; leukocyte activation; microbial; mouse model; neovascularization; pathogen; pup; receptor; receptor function; response; tau Proteins; trafficking; tumor growth

DESCRIPTION (provided by applicant): The host response against microbial pathogens consists of the integrated actions of both the innate and adaptive immune systems. Protective immunity to viruses is dependent upon the complex interactions between cytokines and chemokines to regulate both innate and adaptive effector functions. It has been shown that the cytokines induced by pathogens may determine the cellular components that get activated by inducing specific chemokines in infected tissue compartments. T lymphocyte activation, particularly CD8+ T cells, are required to limit virus-associated tissue damage and the promotion of viral clearance from MCMV-infected tissues. The protective function of CD8+T cells against MCMV activation is well documented and consists of the production of IFN-? and TNF-? during late acute infection. However the role CD8 T lymphocytes play when they are recruited to sites of infection has not been assessed. It has been shown that MCMV induces the production of the chemokines CXCL9 and CXCL10, two known CXCR3 ligands, in the liver. These are key factors in promoting the recruitment of CD8+ T cells to sites of MCMV in the liver. CXCR3 is expressed on the surface of CD8+ T cells and a subset of MCMV- specific CD8+ T cells accumulating in the liver during infection. This proposal seeks to determine the significance of CXCL9 and/or CXCL10, in promoting the effector functions of CD8+ T cells during MCMV infection and to investigate the mechanism by which these chemokines modulate the effector functions of CD8 T lymphocytes. We will make use of proliferation and cytoxicity assays to evaluate the effects of CD8+ T cells. ELISAs and flow cytometry analysis will be used to measure ex vivo cytokine and chemokine production. We already have Mig-/-, IP10 -/- and CXCR3 -/- pups that are ready to be used. The results obtained will contribute to the understanding of events that are important for defense of viral infection and will help to define a critical cascade for protection during infection. It will also help to elucidate the chemokine/ chemokine receptor functions in the recruitment of lymphocytes responding to a virus infection in tissue sites.

描述（由申请方提供）：宿主对微生物病原体的反应由先天性和适应性免疫系统的综合作用组成。对病毒的保护性免疫依赖于细胞因子和趋化因子之间复杂的相互作用来调节先天和适应性效应器功能。已经表明，由病原体诱导的细胞因子可以决定通过在感染的组织区室中诱导特异性趋化因子而被激活的细胞组分。T淋巴细胞活化，特别是CD 8 + T细胞，是限制病毒相关组织损伤和促进病毒从MCMV感染组织中清除所必需的。CD 8 +T细胞对MCMV激活的保护功能是有据可查的，包括IFN-？TNF-？晚期急性感染。然而，CD 8 T淋巴细胞在被募集到感染部位时所起的作用尚未评估。已经显示MCMV诱导肝脏中两种已知的CXCR 3配体趋化因子CXCL 9和CXCL 10的产生。这些是促进CD 8 + T细胞募集到肝脏中MCMV位点的关键因素。CXCR 3在CD 8 + T细胞的表面上表达，并且在感染期间在肝脏中积累MCMV特异性CD 8 + T细胞的子集。该提议旨在确定CXCL 9和/或CXCL 10在MCMV感染期间促进CD 8 + T细胞的效应子功能中的意义，并研究这些趋化因子调节CD 8 T淋巴细胞的效应子功能的机制。我们将利用增殖和细胞毒性试验来评估CD 8 + T细胞的作用。ELISA和流式细胞术分析将用于测量离体细胞因子和趋化因子产生。我们已经有米格-/-，IP 10-/-和CXCR 3-/-的小狗，准备使用。所获得的结果将有助于理解对病毒感染防御重要的事件，并将有助于定义感染期间保护的关键级联。这也将有助于阐明趋化因子/趋化因子受体在组织部位中应答病毒感染的淋巴细胞募集中的功能。