An improved mouse model for aging immunology
改进的衰老免疫学小鼠模型
基本信息
- 批准号:9332619
- 负责人:
- 金额:$ 29.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-03-15 至 2019-02-28
- 项目状态:已结题
- 来源:
- 关键词:AcuteAcute respiratory infectionAddressAdoptive TransferAdultAgeAgingAntigensBiological AssayCellsChronicCytomegalovirusDataDevelopmentElderlyEpitopesExhibitsExperimental ModelsFemaleGene ExpressionGene Expression ProfileGenetic TranscriptionGoalsHouse miceHumanHuman Herpesvirus 4ImmuneImmune System DiseasesImmune System and Related DisordersImmune responseImmune systemImmunityImmunologicsImmunologyIndividualInfectionInfluenzaIntestinal parasiteLifeLongevityMHC antigenMemoryMicrobeModelingMolecular ProfilingMusNatureNematospiroides dubiusPhenotypePhysiologicalPopulationQuality of lifeResearchSendai virusStudy modelsT cell responseT memory cellT-LymphocyteTestingTherapeutic InterventionVaccinationVaccinesVirusagedcross reactivitycytokineexperienceexperimental studygerm free conditionimmune functionimprovedinflammatory markerinfluenzavirusmalemiddle agemouse modelneonatal humanpathogenpre-clinicalresponsesenescencevaccination strategy
项目摘要
Immune function declines with age. In order to extend quality of life, it is critical that we
understand mechanisms underlying the age-associated decline in immune function. Humans
are riddled throughout life with a variety of acute and chronic infections which trigger the
immune system. The accumulating effect of acute and chronic infections throughout the lifespan
profoundly impacts the T cell repertoire and immune response of aged individuals. Although the
aging mouse model provides a robust experimental model amenable to addressing
mechanisms, it is increasingly realized that an important limitation of the mouse model is that
mice are typically housed in specific pathogen free conditions. Immune senescence cannot be
appropriately modeled in mice in which antigen experience has been deliberately constrained.
In addition, optimal immune responses to new infections are thought to be dependent on a
diverse repertoire of naïve T cells. With age, the numbers and diversity of naïve T cells decline
and the ratio of memory to naïve T cells greatly increases. It has been determined that T cell
recognition of antigen/MHC is highly degenerate and T cell responses exhibit extensive and
unexpected cross reactivity. We hypothesize that, with the declining numbers of naïve T cells
with age, the response to new infections become increasingly dependent on memory cells that
accumulated with antigen experience and are fortuitously cross reactive. The first goal of this
proposal is to develop a better mouse model for aging by defined exposure early in life to
sequential infection with chronic and acute viruses. The second goal of this developmental R21
is to test the hypothesis that sequentially-infected aged mice, by virtue of enhanced antigen
experience, will manifest increased diversity in the memory T cell repertoire capable of cross-
reacting with new infections. Accomplishing the goals of this developmental R21 will be an
important advance for aging research. Studies in antigen-experienced aged mice will benefit
understanding the impact of antigen experience on immunity and senescence in elderly humans
and has important implications for vaccination strategies for the elderly, supporting the concept
that vaccines in young and middle age are important for maintaining immunity in later life.
免疫功能随着年龄的增长而下降。为了延长生活质量,至关重要的是我们
了解与年龄相关的免疫功能下降的机制。人类
一生中都饱受各种急性和慢性感染的困扰,这些感染会引发
免疫系统。急性和慢性感染在整个生命周期中的累积效应
深刻影响老年人的 T 细胞库和免疫反应。虽然
衰老小鼠模型提供了一个稳健的实验模型,可以解决以下问题
机制,人们越来越认识到小鼠模型的一个重要局限性是
小鼠通常被安置在无特定病原体的条件下。免疫衰老不能
在小鼠中适当建模,其中抗原体验已被故意限制。
此外,对新感染的最佳免疫反应被认为取决于
幼稚 T 细胞的多样性。随着年龄的增长,幼稚 T 细胞的数量和多样性下降
并且记忆T细胞与幼稚T细胞的比例大大增加。已确定T细胞
抗原/MHC 的识别是高度简并的,T 细胞反应表现出广泛和
意外的交叉反应。我们假设,随着初始 T 细胞数量的减少
随着年龄的增长,对新感染的反应越来越依赖于记忆细胞
积累抗原经验并偶然发生交叉反应。本次的第一个目标
提议是通过在生命早期确定暴露来开发更好的衰老小鼠模型
慢性和急性病毒的连续感染。此次开发的R21的第二个目标
是为了检验这样的假设:依次感染老年小鼠,凭借增强的抗原
经验,将体现出记忆 T 细胞库的多样性增加,能够交叉
对新感染做出反应。实现 R21 发展目标将是
衰老研究的重要进展。对经历过抗原的老年小鼠的研究将受益
了解抗原经历对老年人免疫和衰老的影响
对老年人的疫苗接种策略具有重要影响,支持了这一概念
中青年时期的疫苗对于维持晚年的免疫力很重要。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Marcia A Blackman其他文献
Differential impact of ageing on cellular and humoral immunity to a persistent murine γ-herpesvirus
- DOI:
10.1186/1742-4933-7-3 - 发表时间:
2010-02-02 - 期刊:
- 影响因子:5.600
- 作者:
Eric J Yager;In-Jeong Kim;Michael L Freeman;Kathleen G Lanzer;Claire E Burkum;Tres Cookenham;David L Woodland;Marcia A Blackman - 通讯作者:
Marcia A Blackman
Erratum to: Early dysregulation of the memory CD8+T cell repertoire leads to compromised immune responses to secondary viral infection in the aged
- DOI:
10.1186/1742-4933-10-40 - 发表时间:
2013-10-11 - 期刊:
- 影响因子:5.600
- 作者:
Lisa M Connor;Jacob E Kohlmeier;Lynn Ryan;Alan D Roberts;Tres Cookenham;Adam Quinn;Marcia A Blackman;David L Woodland - 通讯作者:
David L Woodland
Marcia A Blackman的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Marcia A Blackman', 18)}}的其他基金
Aging, T cell repertoire, and cellular immunity to influenza virus
衰老、T 细胞库和对流感病毒的细胞免疫
- 批准号:
8485491 - 财政年份:2011
- 资助金额:
$ 29.7万 - 项目类别:
Aging, T cell repertoire, and cellular immunity to influenza virus
衰老、T 细胞库和对流感病毒的细胞免疫
- 批准号:
8185622 - 财政年份:2011
- 资助金额:
$ 29.7万 - 项目类别:
Aging, T cell repertoire, and cellular immunity to influenza virus
衰老、T 细胞库和对流感病毒的细胞免疫
- 批准号:
8307776 - 财政年份:2011
- 资助金额:
$ 29.7万 - 项目类别:
Aging, T cell repertoire, and cellular immunity to influenza virus
衰老、T 细胞库和对流感病毒的细胞免疫
- 批准号:
8664767 - 财政年份:2011
- 资助金额:
$ 29.7万 - 项目类别:
Immunogenicity and efficacy of genetically engineered gamma-herpesvirus vaccines
基因工程γ-疱疹病毒疫苗的免疫原性和功效
- 批准号:
7943957 - 财政年份:2009
- 资助金额:
$ 29.7万 - 项目类别:
Can persistent gamma-herpesviruses be purged from the host?
持久性伽马疱疹病毒可以从宿主体内清除吗?
- 批准号:
7677077 - 财政年份:2009
- 资助金额:
$ 29.7万 - 项目类别:
Can persistent gamma-herpesviruses be purged from the host?
持久性伽马疱疹病毒可以从宿主体内清除吗?
- 批准号:
7876884 - 财政年份:2009
- 资助金额:
$ 29.7万 - 项目类别:
Immunogenicity and efficacy of genetically engineered gamma-herpesvirus vaccines
基因工程γ-疱疹病毒疫苗的免疫原性和功效
- 批准号:
7852176 - 财政年份:2009
- 资助金额:
$ 29.7万 - 项目类别:
Impact of aging on the T cell repertoire and cellular immunity to influenza virus
衰老对 T 细胞库和流感病毒细胞免疫的影响
- 批准号:
7581328 - 财政年份:2009
- 资助金额:
$ 29.7万 - 项目类别:
相似海外基金
2022 Biology of Acute Respiratory Infection GRC / GRS
2022 急性呼吸道感染生物学 GRC / GRS
- 批准号:
10388659 - 财政年份:2022
- 资助金额:
$ 29.7万 - 项目类别:
The Canadian Severe Acute Respiratory Infection, Prospective, Perpetual Observational Study: Informing Clinical Care and the Public Health Response
加拿大严重急性呼吸道感染前瞻性、永久性观察研究:为临床护理和公共卫生应对提供信息
- 批准号:
462643 - 财政年份:2022
- 资助金额:
$ 29.7万 - 项目类别:
Operating Grants
The Canadian Severe Acute Respiratory Infection, Prospective, Perpetual Observational Study: Informing Clinical Care and the Public Health Response
加拿大严重急性呼吸道感染前瞻性、永久性观察研究:为临床护理和公共卫生应对提供信息
- 批准号:
442907 - 财政年份:2020
- 资助金额:
$ 29.7万 - 项目类别:
Operating Grants
2020 Biology of Acute Respiratory Infection Gordon Research Conference and Gordon Research Seminar
2020急性呼吸道感染生物学戈登研究大会暨戈登研究研讨会
- 批准号:
9913675 - 财政年份:2020
- 资助金额:
$ 29.7万 - 项目类别:
New test for the diagnosis of acute respiratory infection that detects viruses and evaluates host gene expression in a nasal sample
用于诊断急性呼吸道感染的新测试,可检测鼻腔样本中的病毒并评估宿主基因表达
- 批准号:
9809720 - 财政年份:2019
- 资助金额:
$ 29.7万 - 项目类别:
2016 Biology of Acute Respiratory Infection Gordon Research Conference & Gordon Research Seminar
2016年急性呼吸道感染生物学戈登研究会议
- 批准号:
9121654 - 财政年份:2016
- 资助金额:
$ 29.7万 - 项目类别:
2014 Biology of Acute Respiratory Infection Gordon Research Conference and Semina
2014年急性呼吸道感染生物学戈登研究会议及研讨会
- 批准号:
8650427 - 财政年份:2014
- 资助金额:
$ 29.7万 - 项目类别:
Meditation and Exercise for Preventing Acute Respiratory Infection (MEPARI-2)
预防急性呼吸道感染的冥想和运动(MEPARI-2)
- 批准号:
8867144 - 财政年份:2012
- 资助金额:
$ 29.7万 - 项目类别:
Meditation and Exercise for Preventing Acute Respiratory Infection (MEPARI-2)
预防急性呼吸道感染的冥想和运动(MEPARI-2)
- 批准号:
9098602 - 财政年份:2012
- 资助金额:
$ 29.7万 - 项目类别:
2012 Biology of Acute Respiratory Infection Gordon Research Conference
2012年急性呼吸道感染生物学戈登研究会议
- 批准号:
8249190 - 财政年份:2012
- 资助金额:
$ 29.7万 - 项目类别: