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:伊加抗体是抵抗粘膜病原体的重要的第一道防线。针对T细胞依赖性抗原的免疫球蛋白的诱导从属于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肠道微生物群的蛋白质抗原作出反应。我们目前的目标是确定,在体内,哪种类型的T细胞反应是由鼠乳杆菌引起的,同时通过肠道。
我们假设肠道微生物通过粘膜诱导T细胞依赖性体液应答,同时抑制细胞介导的应答。测试这一假设可以导致有效的微生物递送系统的设计。我们将通过确定1)肠道微生物如何引发肠道中的幼稚T细胞和2)记忆T细胞中引发的细胞因子类型来测试这一假设。我们设计了L小鼠表达卵清蛋白表位,其在皮下注射时诱导卵清蛋白特异性T细胞增殖。我们将一小部分卵清蛋白特异性T细胞注射到受体小鼠中,并喂养L。在高数量的murinus。通过用抗-CD 4和抗-T细胞受体单克隆抗体染色受体的细胞悬浮液或组织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建立肠道微生物通过肠道激活T细胞诱导CD 69表达。
在抗原特异性的方式,我们将测试的表型和动力学的跨粘膜T细胞的活化,增殖和分化为产生精氨酸的记忆细胞。总的来说,这项研究将阐明口服抗原递送和分泌性抗体产生之间缺失的环节。这些数据将对人类健康很重要,建立了一个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)
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MASSIMO COSTALONGA其他文献
MASSIMO COSTALONGA的其他文献
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{{ 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
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Calprotectin-mediated CD69 signaling in periodontitis
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$ 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
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10618409 - 财政年份:2021
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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
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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
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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:
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