Tracking Mucosal T cells to Commensal Microbes in Vivo
追踪粘膜 T 细胞与体内共生微生物
基本信息
- 批准号:6845376
- 负责人:
- 金额:$ 25.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-02-01 至 2007-01-31
- 项目状态:已结题
- 来源:
- 关键词:LactobacillusT lymphocytecell differentiationcell proliferationcell typecellular immunityconfocal scanning microscopycytokineenteric bacteriaflow cytometryhost organism interactionhumoral immunityimmune responseimmunoglobulin Aimmunologic memoryimmunoregulationlaboratory mouseleukocyte activation /transformationmolecular shapemucosal immunityoral bacteriaprotein localizationsecretory immune systemvirulence
项目摘要
DESCRIPTION: IgA antibodies provide an important first line of defense against mucosal pathogens. The induction of immunoglobulins against T cell-dependent antigens is subordinate to T cell activation, T/B cell interaction and cytokines. Our long-range goal is to learn how the mucosal immune system responds to protein antigens of the virulent and commensal microbiota. Our current objective is to determine, in vivo, which type of T cell response is induced by the commensal Lactobacillus murinus, while transiting the intestine.
We hypothesize that intestinal commensal microorganisms transmucosally induce a T cell-dependent humoral response, while suppressing the cell-mediated response. Testing this hypothesis can lead to the design of effective microbial delivery systems. We will test this hypothesis by determining 1) how a commensal microbe primes naive T cells in the intestine and 2) the type of cytokines elicited in memory T cells. We engineered L. murinus to expresses an ovalbumin epitope that induces ovalbumin-specific T cell proliferation when injected subcutaneously. We inject a small population of ovalbumin-specific T cells into recipient mice and feed L. murinus in high numbers. Ovalbumin-specific T cells are tracked by staining cell suspensions or tissues of the recipients with anti-CD4 and an anti-T cell receptor monoclonal antibody. Four-color flow cytometry and confocal immunohistology will establish in vivo that commensal microorganisms transiting the intestine activate T cells to induce CD69 expression.
In an antigen-specific manner we will test the phenotype and kinetics of transmucosal T cell activation, proliferation and differentiation into cytokine-producing memory cells. Collectively, this research will elucidate the missing link between the oral antigen delivery and the production of secretory antibodies. The data will be important to human health, establishing a framework to study in vivo mucosal infectious agents and oral vaccines.
描述:IgA 抗体提供了针对粘膜病原体的重要第一道防线。针对 T 细胞依赖性抗原的免疫球蛋白的诱导服从于 T 细胞活化、T/B 细胞相互作用和细胞因子。我们的长期目标是了解粘膜免疫系统如何对有毒和共生微生物群的蛋白质抗原做出反应。我们当前的目标是确定体内共生鼠乳杆菌在通过肠道时诱导哪种类型的 T 细胞反应。
我们假设肠道共生微生物跨粘膜诱导 T 细胞依赖性体液反应,同时抑制细胞介导的反应。检验这一假设可以设计出有效的微生物输送系统。我们将通过确定 1) 共生微生物如何启动肠道中的幼稚 T 细胞和 2) 记忆 T 细胞中引发的细胞因子类型来检验这一假设。我们对 L. murinus 进行了改造,使其表达卵清蛋白表位,皮下注射时可诱导卵清蛋白特异性 T 细胞增殖。我们将一小群卵清蛋白特异性 T 细胞注射到受体小鼠体内,并喂养大量小鼠乳杆菌。通过用抗 CD4 和抗 T 细胞受体单克隆抗体对受体的细胞悬液或组织进行染色来追踪卵清蛋白特异性 T 细胞。四色流式细胞术和共聚焦免疫组织学将在体内确定穿过肠道的共生微生物激活 T 细胞以诱导 CD69 表达。
我们将以抗原特异性的方式测试跨粘膜 T 细胞活化、增殖和分化为产生细胞因子的记忆细胞的表型和动力学。总的来说,这项研究将阐明口服抗原递送和分泌抗体产生之间缺失的联系。这些数据对人类健康非常重要,建立了研究体内粘膜感染因子和口服疫苗的框架。
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 }}
MASSIMO COSTALONGA其他文献
MASSIMO COSTALONGA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('MASSIMO COSTALONGA', 18)}}的其他基金
Calprotectin and CD69 affect regulatory T cell responses in periodontal disease
钙卫蛋白和 CD69 影响牙周病中调节性 T 细胞反应
- 批准号:
10353423 - 财政年份:2021
- 资助金额:
$ 25.99万 - 项目类别:
Calprotectin and CD69 affect regulatory T cell responses in periodontal disease
钙卫蛋白和 CD69 影响牙周病中调节性 T 细胞反应
- 批准号:
10217424 - 财政年份:2021
- 资助金额:
$ 25.99万 - 项目类别:
Calprotectin-mediated CD69 signaling in periodontitis
牙周炎中钙卫蛋白介导的 CD69 信号传导
- 批准号:
10298399 - 财政年份:2021
- 资助金额:
$ 25.99万 - 项目类别:
Calprotectin-mediated CD69 signaling in periodontitis
牙周炎中钙卫蛋白介导的 CD69 信号传导
- 批准号:
10437044 - 财政年份:2021
- 资助金额:
$ 25.99万 - 项目类别:
Calprotectin-mediated CD69 signaling in periodontitis
牙周炎中钙卫蛋白介导的 CD69 信号传导
- 批准号:
10618409 - 财政年份:2021
- 资助金额:
$ 25.99万 - 项目类别:
MHC-II deficient Langerhans cells with compensatory Tc17 plasticity in oral candidiasis
MHC-II 缺陷朗格汉斯细胞在口腔念珠菌病中具有补偿性 Tc17 可塑性
- 批准号:
10194461 - 财政年份:2020
- 资助金额:
$ 25.99万 - 项目类别:
MHC-II deficient Langerhans cells with compensatory Tc17 plasticity in oral candidiasis
MHC-II 缺陷朗格汉斯细胞在口腔念珠菌病中具有补偿性 Tc17 可塑性
- 批准号:
10056498 - 财政年份:2020
- 资助金额:
$ 25.99万 - 项目类别:
Gingival Langerhans cells regulate plasticity of P. gingivalis-specific T cells
牙龈朗格汉斯细胞调节牙龈卟啉单胞菌特异性 T 细胞的可塑性
- 批准号:
9165057 - 财政年份:2016
- 资助金额:
$ 25.99万 - 项目类别:
P. gingivalis-specific T cells in mice prone and resistant to periodontitis
易患牙周炎和抵抗牙周炎的小鼠体内牙龈卟啉单胞菌特异性 T 细胞
- 批准号:
8507349 - 财政年份:2013
- 资助金额:
$ 25.99万 - 项目类别:
P. gingivalis-specific T cells in mice prone and resistant to periodontitis
易患牙周炎和抵抗牙周炎的小鼠体内牙龈卟啉单胞菌特异性 T 细胞
- 批准号:
8654333 - 财政年份:2013
- 资助金额:
$ 25.99万 - 项目类别:
相似海外基金
Modulation of T lymphocyte Activation by Ã2-Adrenergic Receptor Signalling Pathways
α2-肾上腺素能受体信号通路对 T 淋巴细胞激活的调节
- 批准号:
RGPIN-2019-06980 - 财政年份:2022
- 资助金额:
$ 25.99万 - 项目类别:
Discovery Grants Program - Individual
A precision tumor neoantigen identification pipeline for cytotoxic T-lymphocyte-based cancer immunotherapies
用于基于细胞毒性 T 淋巴细胞的癌症免疫疗法的精准肿瘤新抗原识别流程
- 批准号:
10581488 - 财政年份:2022
- 资助金额:
$ 25.99万 - 项目类别:
Modulation of T lymphocyte Activation by ß2-adrenergic Receptor Signalling Pathways
α2-肾上腺素能受体信号通路对 T 淋巴细胞激活的调节
- 批准号:
574979-2022 - 财政年份:2022
- 资助金额:
$ 25.99万 - 项目类别:
University Undergraduate Student Research Awards
A precision tumor neoantigen identification pipeline for cytotoxic T-lymphocyte-based cancer immunotherapies
用于基于细胞毒性 T 淋巴细胞的癌症免疫疗法的精准肿瘤新抗原识别流程
- 批准号:
10332251 - 财政年份:2022
- 资助金额:
$ 25.99万 - 项目类别:
Modulation of T lymphocyte Activation by Ã2-adrenergic Receptor Signalling Pathways
α2-肾上腺素能受体信号通路对 T 淋巴细胞激活的调节
- 批准号:
574984-2022 - 财政年份:2022
- 资助金额:
$ 25.99万 - 项目类别:
University Undergraduate Student Research Awards
Modulation of T lymphocyte Activation by ß2-adrenergic Receptor Signalling Pathways
α2-肾上腺素能受体信号通路对 T 淋巴细胞激活的调节
- 批准号:
574985-2022 - 财政年份:2022
- 资助金额:
$ 25.99万 - 项目类别:
University Undergraduate Student Research Awards
Modulation of T lymphocyte Activation by Ã2-adrenergic Receptor Signalling Pathways
α2-肾上腺素能受体信号通路对 T 淋巴细胞激活的调节
- 批准号:
574978-2022 - 财政年份:2022
- 资助金额:
$ 25.99万 - 项目类别:
University Undergraduate Student Research Awards
Investigating the cell-based activity of a new class of cytotoxic T-lymphocyte antigen-4 (CTLA-4) small molecule inhibitors
研究一类新型细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 小分子抑制剂的细胞活性
- 批准号:
444149 - 财政年份:2021
- 资助金额:
$ 25.99万 - 项目类别:
Operating Grants
Novel pathways in T lymphocyte differentiation and function
T 淋巴细胞分化和功能的新途径
- 批准号:
RGPIN-2015-05491 - 财政年份:2021
- 资助金额:
$ 25.99万 - 项目类别:
Discovery Grants Program - Individual
Modulation of T lymphocyte Activation by ß2-Adrenergic Receptor Signalling Pathways
通过 α2-肾上腺素能受体信号通路调节 T 淋巴细胞激活
- 批准号:
RGPIN-2019-06980 - 财政年份:2021
- 资助金额:
$ 25.99万 - 项目类别:
Discovery Grants Program - Individual














{{item.name}}会员




