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Mechanisms of CD4 T cell help for CD8 T cells during persistent viral infection

CD4 T 细胞在持续病毒感染期间帮助 CD8 T 细胞的机制

基本信息

批准号：
8256353
负责人：
Jeffrey Scott Hale
金额：
$ 5.39万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8256353
关键词：
Antigens CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cell Communication Cell Lineage Cell physiology Cells Characteristics Chronic Complex Differentiation Antigens Equilibrium Failure Functional disorder Gene Expression Genes Genetic Programming Goals HIV Helper-Inducer T-Lymphocyte Hepatitis B Hepatitis C Immune response Immune system Infection Invaded Lymphocytic choriomeningitis virus Mediating Modeling Molecular Mus Nature Play Production Receptor Signaling Recovery Signal Transduction Source Structure of germinal center of lymph node T cell response T-Lymphocyte Testing Therapeutic Therapeutic Intervention Vaccine Design Vaccines Viral Viral Antigens Viral Physiology Virus Virus Diseases cytokine cytotoxicity design exhaust exhaustion human disease improved improved functioning in vivo insight interleukin-21 receptor memory CD4 T lymphocyte programs receptor receptor expression research study response treatment strategy tumor

项目摘要

Following viral challenge, failure of the immune system to control and eliminate virus results in chronic infection. In many chronic viral infection, viral persistence drives the loss of T cell function, termed "exhaustion". T cell exhaustion represents an obstacle to the treatment and clearance of many viral infections and tumors. A complex genetic program regulates the expression of inhibitory receptors by exhausted T cells, and signaling through these receptors mediates their poor anti-viral function. CD4 T cells play a key role in providing help, through direct cell-cell interactions, or through the secretion of solule factors, to maintain the anti-viral function of CD8 cells during chronic viral infection, allowing or improved viral control. The objective of this study is to determine the cellular and molecular mechanisms for CD4 help provided to CD8 T cells during chronic viral infection. The well- characterized lymphocytic choriomeningitis virus (LCMV) will be used to investigate the contribution of CD4 T cells following severe CD8 T cell exhaustion in chronically infected mice. These experiments will be used to determine the functional characteristics and relevant CD4 T helper lineage of cells that provide optimal help to CD8 T cells during chronic LCMV infection. Furthermore, the functional and molecular program that regulates the restored anti-viral function of CD8 T cells that receive help from CD4 T cells during chronic infection will be investigated.

在病毒攻击后，免疫系统控制和消除病毒的失败导致慢性感染。在许多慢性病毒感染中，病毒的持续存在导致T细胞功能丧失，称为“衰竭”。T细胞衰竭是许多病毒感染和肿瘤治疗和清除的障碍。一个复杂的遗传程序通过耗尽的T细胞调节抑制性受体的表达，并通过这些受体介导其不良的抗病毒功能。在慢性病毒感染期间，CD4 T细胞通过直接的细胞间相互作用，或通过分泌溶质因子，维持CD8细胞的抗病毒功能，允许或改善病毒控制，在提供帮助方面发挥关键作用。本研究的目的是确定CD4在慢性病毒感染期间向CD8 T细胞提供帮助的细胞和分子机制。淋巴细胞性脉络丛脑膜炎病毒（LCMV）将被用来研究慢性感染小鼠严重CD8 T细胞衰竭后CD4 T细胞的贡献。这些实验将用于确定在慢性LCMV感染期间为CD8 T细胞提供最佳帮助的细胞的功能特征和相关CD4 T辅助谱系。此外，在慢性感染期间，CD8 T细胞在接受CD4 T细胞的帮助下恢复抗病毒功能，调控其功能和分子程序将被研究。