Analyses of the effects of pro-inflammatory cytokines on CD4+ T cell responses

促炎细胞因子对 CD4 T 细胞反应的影响分析

基本信息

批准号：
7653812
负责人：
JASON Kyle WHITMIRE
金额：
$ 12.4万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-15 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7653812
关键词：
Address Adoptive Transfer Affect Antigens Antiviral Agents Antiviral Response Apoptosis Applications Grants B-Lymphocytes Breeding CD4 Positive T Lymphocytes CD8B1 gene Cell Count Cell Differentiation process Cell Survival Cell division Cells Cellular biology Chronic Cytokine Signaling Cytotoxic T-Lymphocytes Data Development Disease Disease Outbreaks Genes Glean Goals Grant HIV Health Benefit Helper-Inducer T-Lymphocyte Hepatitis C virus Humoral Immunities Immune Immune response Immunity Individual Infection Inflammation Inflammatory Interferons Investigation Knowledge Lead Leukocytes Lung Lymphocyte Lymphocytic choriomeningitis virus Memory Memory B-Lymphocyte Modeling Molecular Mouse Strains Multidrug-Resistant Tuberculosis Mus Pathway interactions Phase Phase III Clinical Trials Play Population Principal Investigator Process Public Health Publications Recombinants Research Research Institute Resources Role Scientist Severe Acute Respiratory Syndrome Signal Transduction Specificity Stifle joint T cell regulation T memory cell T-Cell Development T-Lymphocyte Techniques Testing Time Vaccination Vaccine Design Vaccines Virus Virus Activation Virus Diseases Work clinically relevant cytokine experience improved in vivo interest memory CD4 T lymphocyte novel pandemic influenza pathogen precursor cell programs prophylactic public health relevance research study response single molecule vaccine efficacy

项目摘要

DESCRIPTION (provided by applicant): There is a void in our understanding of how CD4 T cell responses are generated and maintained. This proposal is aimed at filling this void, by characterizing how pro- inflammatory cytokines govern the initial virus-specific lymphocyte response after infection and the differentiation of memory cells. The underlying hypothesis of this grant is that inflammatory signals enhance primary and memory T cell development. This will be tested by pursuing three specific aims: 1) to determine how IFN? signals increase the peak CD4 T cell response and memory, 2) to characterize early T cell competition for pro-inflammatory cytokines that affect memory cell differentiation, and 3) to establish the mechanism(s) by which IFN? sustains CD4 T cell responses during chronic virus infection. The proposed experiments address fundamental aspects of CD4 T cell control and memory cell differentiation. Information gleaned from these studies will further investigations directed at understanding CD4 T cell regulation of CD8 T cell memory and B cell memory. The long-range research goals are to eventually identify specific molecular pathways that can be pharmacologically targeted to enhance vaccine-induced T cell memory. PUBLIC HEALTH RELEVANCE Vaccines protect against infection by increasing the number of pathogen-specific white blood cells. These studies investigate how interferons increase the number of these cells. These experiments will hopefully identify new ways to improve vaccines.

描述（由申请人提供）：我们对CD4 T细胞响应的产生和维护的理解有一个空白。该建议旨在通过表征促炎性细胞因子如何控制感染后初始病毒特异性淋巴细胞反应和记忆细胞分化的初始病毒特异性淋巴细胞反应来填补这一空隙。该赠款的基本假设是炎症信号增强了原发性和记忆T细胞的发育。这将通过追求三个具体目标来测试：1）确定如何进行IFN？信号增加了CD4 T细胞响应和记忆的峰值，2）表征会影响记忆细胞分化的促炎细胞因子的早期T细胞竞争，以及3）建立IFN的机制？在慢性病毒感染过程中持续CD4 T细胞反应。提出的实验介绍了CD4 T细胞控制和记忆细胞分化的基本方面。从这些研究中收集的信息将进一步研究旨在了解CD8 T细胞记忆和B细胞记忆的CD4 T细胞调节。远程研究目标是最终确定可以针对药理靶向的特定分子途径，以增强疫苗诱导的T细胞记忆。公共卫生相关性疫苗通过增加病原体特异性白细胞的数量来预防感染。这些研究研究了干扰素如何增加这些细胞的数量。这些实验将有望确定改善疫苗的新方法。