Impact of allergy and seasonality on lymphokine producing T cells

过敏和季节性对产生淋巴因子的 T 细胞的影响

• 批准号: 8325206
• 负责人: Alessandro Sette
• 金额: $ 26.67万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325206
• 关键词: Allergens; Allergic Disease; Allergic rhinitis; Asthma; Biological Assay; Breathing; Cell physiology; Cells; Clinical; Complement; Complex; Complication; Contracts; Controlled Environment; Data; Disease; Disease Progression; Dose; Epitopes; Equilibrium; Exposure to; Felis catus; Goals; Hypersensitivity; Immune response; Immunodominant Epitopes; In Vitro; Individual; Instruction; Longitudinal Studies; Lymphokines; Modeling; Nose; Pattern; Phenotype; Phleum; Population; Production; Protein Fragment; Pyroglyphidae; Reagent; Relative (related person); Rhinitis; Sampling; Seasons; Series; Severities; Source; Staging; Staining method; Stains; Symptoms; T cell response; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Time; Validation; cytokine; design; enzyme linked immunospot assay; grass pollen; prevent; programs; research study; response; tissue culture

PROJECT SUMMARY (See instructions): Two of the RFA main goals are the characterization of epitopes derived from the Large Scale Allergen Epitope Identification Contracts, 1) as a function of seasonality and 2) disease progression. Accordingly, we propose to test the hypothesis that different stages (in-season versus out-of-season), types (rhinitis versus asthma) and severities of allergic disease are associated with not only differential magnitude of T cell responses, but also distinctive patterns in terms of the TH subsets involved and their interplay. We will focus on immunodominant regions from three important allergens, namely timothy grass (TG), house dust mite (HDM) and cat dander (CD). In our first Aim, we propose to characterize responses in moderate/severe (MO/SA) and mild asthmatics (MA), and contrast them with those observed in non-asthmatic individuals suffering from allergic rhinitis (AR). Preliminary data suggest that differential ILIO, ILI7 and IFNy production correlate with different disease states. Here, we propose to characterize the subsets of TH cells producing these lymphokines ex vivo and following in vitro stimulation, by ELISPOT, intracellular cytokine staining (ICS) and tetramer staining assays. We will further examine whether the different subsets are distinct or can originate from each other in vitro, because of TH cell plasticity. Preliminary data also suggest that the relative balance of TH subsets differs substantially when TG and HDM responses are compared. We will therefore investigate whether different distributions of TH subsets correlate with allergen source. Our preliminary data further highlights dramatic differences in magnitude of TG responses as a function of seasonal exposure. In the second Aim we propose to determine in longitudinal studies response magnitude and TH functional subsets. In a further series of experiments we will perform challenge studies utilizing TG pollen extracts. We expect that because of a more vigorous response TH cells might be more easily detectable ex vivo, and characterized in greater detail without potential alterations introduced by in vitro culture. These studies will characterize the functional T cell subsets involved in different disease settings and as a function of seasonality.

项目摘要（参见说明）： RFA 的两个主要目标是对源自大规模过敏原表位识别合同的表位进行表征，1) 作为季节性的函数，2) 疾病进展。因此，我们建议检验以下假设：过敏性疾病的不同阶段（季节内与淡季）、类型（鼻炎与哮喘）和严重程度不仅与 T 细胞反应的不同程度相关，而且与所涉及的 TH 亚群及其相互作用方面的独特模式有关。我们将重点关注三种重要过敏原的免疫优势区域，即梯牧草 (TG)、屋尘螨 (HDM) 和猫皮屑 (CD)。在我们的第一个目标中，我们建议将反应描述为中度/重度 （MO/SA）和轻度哮喘患者（MA），并将其与非哮喘个体中观察到的结果进行对比 患有过敏性鼻炎（AR）。初步数据表明，ILIO、ILI7 和 IFNy 的产生差异 与不同的疾病状态相关。在这里，我们建议表征产生的 TH 细胞亚群 这些淋巴因子离体并在体外刺激后，通过 ELISPOT、细胞内细胞因子染色 (ICS) 和四聚体染色测定。我们将进一步检查不同的子集是否是不同的或可以 由于 TH 细胞的可塑性，它们在体外相互起源。初步数据还表明，相对 当比较 TG 和 HDM 响应时，TH 子集的平衡存在显着差异。因此我们将 研究 TH 子集的不同分布是否与过敏原来源相关。我们的初步数据 进一步强调了 TG 反应幅度作为季节暴露函数的显着差异。在第二个目标中，我们建议在纵向研究中确定响应幅度和 TH 功能子集。在进一步的系列实验中，我们将利用 TG 花粉提取物进行挑战研究。我们预计，由于反应更加强烈，TH 细胞可能更容易在体外检测到，并且 更详细地表征，没有体外培养引入的潜在改变。这些研究将描述不同疾病环境中涉及的功能性 T 细胞亚群的特征，并作为季节性的函数。