IL-10/IL10R in the Regulation of Self-Reactive CTL by CD8+ T-cells
IL-10/IL10R 在 CD8 T 细胞调节自身反应性 CTL 中的作用
基本信息
- 批准号:9223809
- 负责人:
- 金额:$ 23.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-06 至 2018-11-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdoptive TransferAnimalsAntigen PresentationAntigensAutoimmune DiseasesAutoimmune ProcessAutoimmunityCD8-Positive T-LymphocytesCD8B1 geneCancer PatientCell LineageCell physiologyCellsCellular ImmunityCharacteristicsChickensComplexCytotoxic T-LymphocytesDendritic CellsDevelopmentEffector CellElementsEnvironmentEquilibriumExperimental ModelsFamily PicornaviridaeFutureGene ExpressionGenerationsGeneticGoalsHomeostasisIL10 geneIL2 geneImmuneImmune responseImmune systemImmunityImmunocompetentImmunosuppressionInflammationInflammatoryInformal Social ControlInsulinInterferon Type IIInterleukin-10InvestigationKnowledgeLearningMaintenanceMalignant NeoplasmsMature T-LymphocyteMediatingMemoryModelingMolecularMusOVA-8OvalbuminPancreasPancreatic InjuryPatientsPhenotypePlayPopulationProcessProductionProtocols documentationRattusRecruitment ActivityRegulationRegulatory T-LymphocyteReporterReportingResolutionRoleSchemeSourceSpleenStructureSuppressor-Effector T-LymphocytesSurfaceSystemT-Cell Antigen Receptor SpecificityT-Cell ReceptorT-LymphocyteTestingTherapeuticTissuesTransgenesVaccinationVirusWorkautoreactivitybasecell growthcellular targetingcytokinecytotoxicityimmune system functionimmunoregulationin vitro Modelin vivoinsightkillingsperforinphenotypic biomarkerpromoterreceptorresponsevector-induced
项目摘要
PROJECT SUMMARY/ABSTRACT
CD8+ suppressor T-cells play important roles in the maintenance of immune homeostasis. However, the
phenotypic and functional characteristics of these cells remains poorly characterized relative to their CD4
regulatory T cell counterparts, even though some evidence suggests CD8 regulators can be more important
than CD4 T regulatory cells. We have been investigating the cellular determinants limiting autoimmune attack
in mice against otherwise healthy tissue by introducing and activating self-reactive T cells into a normally
tolerant and regulated environment. A key finding is that inflammation in the tissue is quickly extinguished
limiting cellular damage to vital structures. Early in the inflammatory process immune cells from the tolerant
repertoire are recruited into the tissues harboring autoimmune CTL. Using genetic depletion strategies, we
learned that CD8+ regulators are more critical to limiting autoimmune attack in this setting than are CD4+
regulators. Importantly, regulation can be restored in our model by adoptive transfer of CD8+ spleen cells from
otherwise unmanipulated animals. This approach identified IL10 and perforin as critical factors determining the
ability to limit the damage by autoimmune attack. However, we failed to find evidence of IL10 gene expression
the CD8 “regulatory” cell population in inflamed tissue using an IL10 reporter suggesting that IL10 may act
earlier in the process. Furthermore, we found that fixing the T cell receptor specificity of the regulatory
population did not ablate their ability to limit autoimmune attack. Accordingly, we have developed the
overarching hypothesis that IL10 is essential for the generation of CD8+ suppressor cells and that the
mechanism of suppression is through a perforin-dependent killing or inactivation of antigen specific effector T-
cells mediated through a TcR independent recognition process. In this study, we seek to acquire needed
fundamental information about the role IL10 in the generation and function of CD8 regulatory T cells. Our
approach will be to (1) identify the cellular surface phenotypic markers associated with the regulatory cells, (2)
identify important sources of IL10 in the generation and function of these CD8 regulatory T cells, and (3) learn
where and when these regulatory cells are formed. Along the way we will examine alternative in vitro models
to enable efficient definition of the molecular mechanisms giving rise to CD8 regulators and to their ability to
limit the functions of activated CTL. Understanding the basis of this strong immune regulatory function could
provide insights into how to augment or limit CTL attack for the benefit of cancer or autoimmune disease
patients, respectively.
项目摘要/摘要
CD8+抑制性T细胞在维持免疫稳态中起着重要作用。然而,
这些细胞的表型和功能特征与它们的CD4相比仍然很差
调节性T细胞对应物,尽管一些证据表明CD8调节器可能更重要
而不是CD4T调节细胞。我们一直在研究限制自身免疫攻击的细胞决定因素。
通过将自身反应性T细胞引入并激活正常的
宽容和规范的环境。一个关键的发现是,组织中的炎症很快就会消失
将细胞损伤限制在重要结构上。在炎症过程的早期,免疫细胞从耐受
谱系被招募到含有自身免疫性CTL的组织中。使用基因枯竭策略,我们
了解到在这种情况下,CD8+调节器在限制自身免疫攻击方面比CD4+更关键
监管者。重要的是,在我们的模型中,通过过继转移CD8+脾细胞可以恢复调节
否则就是不受操控的动物。这种方法确定IL-10和穿孔素是决定
能够限制自身免疫攻击造成的伤害。然而,我们未能找到IL10基因表达的证据
炎症组织中CD8“调节”细胞群使用IL10记者暗示IL10可能起作用
在这个过程的早些时候。此外,我们还发现,固定T细胞受体的调节性
人群并没有削弱他们限制自身免疫攻击的能力。因此,我们开发了
最重要的假设是,IL10对于CD8+抑制细胞的产生是必不可少的,并且
抑制的机制是通过穿孔素依赖的杀伤或灭活抗原特异性效应器T-
细胞通过TCR非依赖的识别过程介导。在这项研究中,我们寻求获得所需的
关于IL10在CD8调节性T细胞的产生和功能中的作用的基本信息。我们的
方法将是(1)识别与调节细胞相关的细胞表面表型标记,(2)
确定在这些CD8调节性T细胞的产生和功能中IL10的重要来源,以及(3)了解
这些调控细胞在何时何地形成。在此过程中,我们将研究替代的体外模型
为了能够有效地定义产生CD8调节器的分子机制及其能力
限制激活的CTL的功能。了解这种强大的免疫调节功能的基础可能会
提供有关如何增强或限制CTL攻击以利于癌症或自身免疫性疾病的见解
分别为患者。
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 }}
LARRY R PEASE其他文献
LARRY R PEASE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('LARRY R PEASE', 18)}}的其他基金
Blocking airway inflammation with B7-DC cross-linking Ab
使用 B7-DC 交联抗体阻断气道炎症
- 批准号:
7036883 - 财政年份:2006
- 资助金额:
$ 23.85万 - 项目类别:
Blocking airway inflammation with B7-DC cross-linking Ab
使用 B7-DC 交联抗体阻断气道炎症
- 批准号:
7166813 - 财政年份:2006
- 资助金额:
$ 23.85万 - 项目类别:
Blocking airway inflammation with B7-DC cross-linking Ab
使用 B7-DC 交联抗体阻断气道炎症
- 批准号:
7331495 - 财政年份:2006
- 资助金额:
$ 23.85万 - 项目类别:
Blocking airway inflammation with B7-DC cross-linking Ab
使用 B7-DC 交联抗体阻断气道炎症
- 批准号:
7544476 - 财政年份:2006
- 资助金额:
$ 23.85万 - 项目类别:
Promoting Tumor Immunity by Cross-Linking B7-DC
通过交联 B7-DC 促进肿瘤免疫
- 批准号:
7176218 - 财政年份:2004
- 资助金额:
$ 23.85万 - 项目类别:
Promoting Tumor Immunity by Cross-linking B7-DC
通过交联 B7-DC 促进肿瘤免疫
- 批准号:
8387014 - 财政年份:2004
- 资助金额:
$ 23.85万 - 项目类别:
Promoting Tumor Immunity by Cross-linking B7-DC
通过交联 B7-DC 促进肿瘤免疫
- 批准号:
7577266 - 财政年份:2004
- 资助金额:
$ 23.85万 - 项目类别:
Promoting Tumor Immunity by Cross-Linking B7-DC
通过交联 B7-DC 促进肿瘤免疫
- 批准号:
6859413 - 财政年份:2004
- 资助金额:
$ 23.85万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Research Grant