Mast cells' contribution to T cell immunity

肥大细胞对 T 细胞免疫的贡献

• 批准号: 7432256
• 负责人: Melissa A Brown
• 金额: $ 37.75万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7432256
• 关键词: Affect; Allergic; Antigens; Arthritis; Attenuated; Bacterial Infections; Biological Models; CD4 Positive T Lymphocytes; CD44 gene; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell Maturation; Cell physiology; Cell surface; Cells; Class; Coculture Techniques; Data; Dendritic Cells; Employee Strikes; Environment; Epitopes; Event; Experimental Autoimmune Encephalomyelitis; Gene Expression; Generations; Genes; Histamine; Immune response; Immune system; Immunity; Immunization; In Vitro; Infection; Inflammatory; Interferon Type II; Interleukin-15; Interleukin-4; Interleukin-7; Kinetics; Knock-in Mouse; Leukotriene B4; Life; Listeria monocytogenes; Lymphocytic choriomeningitis virus; Mediator of activation protein; Membrane Proteins; Memory; Microarray Analysis; Modeling; Multiple Sclerosis; Mus; Myelin; Pathologic; Peptides; Peritoneal; Phenotype; Play; Process; Prostaglandins; Protocols documentation; Recombinants; Regulation; Role; SELL gene; Shapes; Symptoms; System; T memory cell; T-Lymphocyte; TNFRSF5 gene; TNFSF5 gene; Testing; Wild Type Mouse; bacterial resistance; base; cytokine; in vivo; indexing; interleukin-23; mast cell; memory acquisition; migration; reconstitution; research study; response

Mast cells have a well-established role in the inflammatory processes that regulate allergic responses. Recent data have implicated mast cells in a variety of other pathologic and protective immune responses. These include exacerbation of symptoms in murine models of multiple sclerosis (Experimental allergic encephalomyelitis - EAE) and arthritis and resistance to bacterial infections. In addition to mediators that are known to affect the recruitment and activation state of cells of the innate immune system, mast cells also express many molecules that have documented effects on the regulation of adaptive immune responses. These include CD40L, IL-2, IL-4, IL-7, IL-15, IL-23, LTB4 and histamine. We recently compared the T cell responses of mast cell-deficient mice (W/Wv) with their wild type littermates after immunization with a myelin peptide in CFA, a protocol used to induce EAE. Although there is no inherent deficit in W/Wv-derived T cells activated in a mast cell-sufficient environment, several indices of activation including stimulation-dependent changes in the expression of CD44, CD11a, CD69 and CD62L are attenuated in T cells primed in a mast cell-deficient setting as is the ability to express IFN gamma. Notably, both the CD4+ and CD8+ T cell responses were consistently and significantly affected. The sub-optimal CDS response may be due to inefficient mast cell-dependent T cell help. Alternatively, it may reflect the more direct influence of mast cells on CD8+ T cells. Using a well-defined Listeria monocytogenes infection model, experiments in this application will test the hypothesis that mast cells contribute to a microenvironment that shapes several events governing CD4+ and CD8+ T cell function. The specific aims are as follows: 1. To determine the effect of mast cell-deficiency on CD4+ and CD8+ T responses after infection with a recombinant L. monocytogenes expressing gp33-41, the class I LCMV epitope (rLM33). 2. To examine the influence of mast cells on dendritic cell maturation, migration and T cell stimulatory function in rl_M33 infected mice. 3. 3. To assess the changes in mast cell phenotype during rLM33 infection and determine their relationship to alterations in T cell responses

肥大细胞在调节过敏反应的炎症过程中具有明确的作用。 最近的数据表明肥大细胞参与了多种其他病理和保护性免疫反应。 这些包括在多发性硬化症的鼠模型中的症状加重（实验过敏性 脑脊髓炎- EAE）和关节炎以及对细菌感染的抗性。除了调解人， 已知肥大细胞影响先天免疫系统细胞的募集和活化状态，肥大细胞还 表达许多分子，这些分子对适应性免疫应答的调节有记录的作用。 这些包括CD 40 L、IL-2、IL-4、IL-7、IL-15、IL-23、LTB 4和组胺。我们最近比较了T细胞 用髓鞘免疫后肥大细胞缺陷小鼠（W/Wv）及其野生型同窝小鼠的反应 CFA中的肽，用于诱导EAE的方案。虽然W/Wv来源的T细胞没有固有缺陷， 在肥大细胞充足的环境中活化，包括刺激依赖性的活化的几个指标 CD 44、CD 11 a、CD 69和CD 62 L表达的变化在肥大细胞中引发的T细胞中减弱， 细胞缺陷的设置是表达IFN γ的能力。值得注意的是，CD 4+和CD 8 + T细胞 反应始终受到显著影响。次优CDS响应可能是由于 低效肥大细胞依赖性T细胞帮助。或者，它可能反映了肥大细胞更直接的影响， CD 8 + T细胞。使用明确定义的单核细胞增生李斯特菌感染模型， 应用程序将测试肥大细胞有助于形成几个微环境的假设 控制CD 4+和CD 8 + T细胞功能的事件。具体目标如下： 1.为了确定肥大细胞缺乏对感染后CD 4+和CD 8 + T细胞反应的影响， 重组L.表达gp 33 -41（I类LCMV表位）的单核细胞增多症（rLM 33）。 2.探讨肥大细胞对树突状细胞成熟、迁移和T细胞刺激性的影响， 在rl_M33感染的小鼠中的功能。 3. 3.评估rLM 33感染期间肥大细胞表型的变化并确定它们之间的关系 T细胞反应的改变

项目成果

The meninges: new therapeutic targets for multiple sclerosis.

• DOI: 10.1016/j.trsl.2014.08.005
• 发表时间: 2015-02
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Russi AE;Brown MA
• 通讯作者: Brown MA