Rejuvenation of the T-cell compartment in aging primates

衰老灵长类动物 T 细胞区室的复兴

基本信息

批准号：
7651979
负责人：
JANKO Z. NIKOLICH
金额：
$ 72.24万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-15 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7651979
关键词：
Adult Affect Age Aging Animals Antibody Formation Attenuated Live Virus Vaccine B-Lymphocytes Blood Bromodeoxyuridine Cause of Death Cell Aging Cell Count Cell Proliferation Cell physiology Cells Cessation of life Charge Clinical Research Communicable Diseases Defect Dyes Elderly Epithelial Goals Growth Factor Homeostasis Human Immune Immune system Immunity Interleukin-7 Intervention Investigation Longevity Macaca mulatta Maintenance Measurement Measures Membrane Memory Modeling Modified Vaccinia Virus Ankara Molecular Monkeys Morbidity - disease rate Output Peripheral Phase Phenotype Play Population Primates Production Protocols documentation Rejuvenation Role Societies Staging Symptoms T memory cell T-Cell Development T-Cell Proliferation T-Cell Receptor-Rearrangement Excision DNA Circles T-Lymphocyte T-Lymphocyte Subsets Testing Text Therapeutic Therapeutic Effect Thymus Gland Translations Vaccination Vaccines age related aged cell age cell type combat cytokine cytotoxicity immunogenic improved juvenile animal keratinocyte growth factor lymph nodes mortality nonhuman primate pathogen public health relevance reconstitution research study response restoration senescence treatment effect

项目摘要

DESCRIPTION (provided by applicant): Aging of the immune system (immune senescence) is accompanied by weakening of immune defense against a wide spectrum of pathogens, particularly those that have not been previously encountered by the host. This clinically correlates with increased morbidity and mortality from infectious diseases, which consistently rank in the top five causes of death amongst those 65 and older. T-cell alterations are amongst the most profound and most consistent changes observed in immune senescence. Age-related deficiencies in T-cell immunity are evident directly, in the form of impaired effector response to pathogens, or indirectly, in the form of increased and inflated memory T-cell pool at the expense of na¿ve T- cells. Correction of T-cell immunity often rectifies symptoms of age-related immune senescence, and it is generally believed that reconstitution of na¿ve T-cells, which are critical for defending us against at the wide spectrum of pathogens. Restoration of the na¿ve T-cell numbers and function is therefore one of the key goals in combating immune aging. The principal goal of this application is to examine in non-human primates whether cytokines/growth factors IL-7 and/or KGF can increase na¿ve T-cell production in the thymus and/or expand na¿ve T cell pools in the periphery. As a corollary, na¿ve T-cell rejuvenation will be tested functionally, by examining the ability of rejuvenating KGF/IL-7 treatment to improve the response of old monkeys to vaccination. Public Health Relevance Statement Elderly are the fastest growing segment of our society, and are inadequately protected against infectious diseases due to the aging of the immune system. Successful completion of these experiments would allow us to proceed with therapy of human immune aging with the ultimate goal to reduce, and eventually eliminate, excessive death and illness of the elderly from infectious diseases.

描述（由适用提供）：免疫系统的衰老（免疫感应）是通过对广泛的病原体的弱化的免疫反应来实现的，尤其是那些以前曾经遇到过的病原体。该临床上与传染病的发病率和死亡率的增加相关，这些疾病始终排在65岁及以上的死亡原因前五名。 T细胞的改变是免疫纪录中观察到的最深刻，最一致的变化之一。 T细胞免疫组织化学中与年龄相关的缺陷直接以效应子对病原体的反应受损的形式，或以增加和膨胀的记忆T细胞池的形式，以NATO T-Cells为代价。 T细胞免疫学的纠正通常会纠正与年龄相关的免疫稳定的症状，并且人们普遍认为，NA¿VVE T细胞的重建对于在广泛的病原体中捍卫我们至关重要。因此，恢复NA¿T细胞数量和功能是对抗免疫老化的关键目标之一。该应用的主要目标是在非人类隐私实践中检查细胞因子/生长因子IL-7和/或kgf是否可以增加胸腺中的Na t-ve t细胞产生和/或扩展周围的Na ve t细胞池。作为推论，将通过检查恢复KGF/IL-7治疗以改善旧猴子对疫苗接种的反应的能力，在功能上测试NA¿T-Cell恢复活力。公共卫生相关性陈述老年人是我们社会增长最快的部分，由于免疫系统的衰老而受到不足的保护。这些实验的成功完成将使我们能够继续治疗人类免疫衰老的治疗，并最终从传染病中消除了老年人的过量死亡和疾病。