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Mechanisms Limiting Neonatal Immunity

限制新生儿免疫力的机制

基本信息

批准号：
10408128
负责人：
Brian David Rudd
金额：
$ 43.79万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10408128
关键词：
Acute Address Adult Age Award Bacteria Brain CD8-Positive T-Lymphocytes Cell Compartmentation Cell physiology Cells Child Chronic Chronic Phase Congenital Abnormality Cytomegalovirus Cytomegalovirus Infections Data Development Disease Experimental Models Failure Generations Gestational Age Goals Grant Hematopoietic stem cells IL7 gene Immune Immune response Immunity Infant Infection Knowledge Life Maintenance Memory Mental Retardation Methods Molecular Morbidity - disease rate Mus Mycobacterium tuberculosis Neonatal Neurological outcome Play Positioning Attribute Prevention Production Proliferating Publishing Research Role Severity of illness Simplexvirus T-Lymphocyte Testing Therapeutic Time Toxoplasma gondii United States Vaccines Viral Virus Virus Diseases Virus Replication Virus Shedding Work acute infection age related base cell behavior chronic infection congenital cytomegalovirus congenital infection disability exhaust hearing impairment immune function improved in utero insight mortality mouse model neonatal immunity neonate novel strategies pathogen receptor response stem stem cell population transmission process treatment strategy

项目摘要

Project Summary / Abstract Cytomegalovirus (CMV) is the most common congenital infection and the leading cause of birth defects in children in the United States. While the urgent need for a vaccine against congenital CMV is widely recognized, the underlying mechanisms responsible for the poor generation and inadequate maintenance of immunity remain undefined, thus compromising our ability to create effective methods for prevention and treatment. The goal of this proposal is to use a murine model of congenital CMV to identify both the mechanisms and consequences of failing to control CMV in early life. Since immune control of CMV is largely dependent upon CD8+ T cells, we have focused our studies on understanding why CD8+ T cells in early life fail to control congenital CMV infection. Based on our published studies and new preliminary data, we hypothesize that neonatal CD8+ T cells have an inherent propensity to become functionally exhausted during CMV infection, leading to prolonged viral shedding and the altered development of the CD8+ T cell compartment. In the first aim, we will determine why neonatal CD8+ T cells fail to control CMV during the acute stage of infection and attempt to revive immune functionality by blocking inhibitory receptors. In the second aim, we will examine why CD8+ T cells made after infection fail to control ongoing viral replication during the latent stage of infection and attempt to limit viral shedding by increasing numbers of naïve T cells with IL-7 therapy. Knowledge from these studies is expected to pave the way for the development of vital preventative and therapeutic strategies against congenital CMV disease.

项目摘要/摘要