TCR CELLS PROMOTE TH2 LINEAGE COMMITMENT AND IGE PRODUC

说明(改编自调查员摘要)：的总体目标 这个项目是为了确定TCR伽马/增量细胞所在的细胞界面 参与对模型蛋白抗原的系统免疫反应， 卵清蛋白(OVA)他们有惊人的结果，TCR伽马/增量细胞是 T细胞和B细胞对卵清蛋白的系统免疫应答 我们的研究使用了哮喘的小鼠模型。卵清蛋白攻击野生型小鼠 表现出明显的过敏性炎症反应，以呼吸道为证据 嗜酸性粒细胞增多和血清IgE升高。这些响应在TCR中被衰减 而在TCRβ/-小鼠中则完全不存在。气道口 TCR6-r受试者对雾化乙酰甲胆碱的反应性也降低 相对于受到挑战的野生型小鼠的动物。对于缺乏TCR的小鼠来说也是如此 在整个生命过程中，或在TCR耗尽的野生型小鼠中，伽马/增量细胞 伽马/德尔塔细胞仅在对气溶胶挑战的召回反应中。这个 应用提示TCRγ/Delta细胞在系统免疫中的作用 对卵清蛋白的反应(经腹腔注射用明矾)通过促进分化 CD4+TCRα/β细胞。这些卵子特异的CD4+细胞然后促进B细胞 分化和免疫球蛋白类转换。视觉化和 列举这些事件将暗示可能的地点和分子事件 由此TCR伽马/德尔塔细胞可以影响免疫反应。观察到的 TCR伽马/增量细胞继续影响细胞的大小 在2或3次免疫或挑战后的体液反应更多 关于记忆性CD4+TCR行为的已知情况令人困惑 α/β细胞和B淋巴细胞。这可能意味着TCR伽马/增量细胞 是OVA特有的，就像TCRα/βB细胞一样，它们表现出 功能性记忆反应。或者，TCR伽马/增量细胞具有相同的 每次暴露时对卵清蛋白的反应，以及这种反应的功能影响 以相同的方式表现出来，无论它是否发生在 对抗原的初级或召回反应。这些研究是第一批 模型系统，其中所有必要的试剂都已组装好，开始 明确TCRγ/Delta细胞在“常规”免疫反应中的作用。 具体地说，他们建议：目标1.确定TCR伽马/增量的影响 CD4+TCRα/β细胞对Th2细胞的承诺。目标2. 确定TCRγ/Delta细胞在B细胞生产中的影响 卵子特异性免疫球蛋白。目的3.确定TCRγ/Delta T细胞是否代表先天T细胞 或对OVA的系统免疫反应的适应性成分。

DESCRIPTION (Adapted from the Investigator's abstract): The overall goal of this project is to determine the cellular interface where TCR gamma/delta cells participate in the systemic immune response to a model protein antigen, Ovalbumin (OVA). They have striking results that TCR gamma/delta cells are potent contributors to the T- and B-cells systemic immune response to OVA from our studies using a mouse model of asthma. Ovalbumin-challenged wildtype mice demonstrate marked allergic inflammatory response, evidenced by airway eosinophilia and elevated serum IgE. These responses are attenuated in TCR gamma -/- animals and completely absent in TCR beta-/- mice. Airway responsiveness to aerosolized methacholine is also reduced in challenged TCR6-r animals relative to challenged wildtype mice. This is true for mice lacking TCR gamma/delta cells throughout life, or in wildtype mice that are depleted of TCR gamma/delta cells only during the recall response to aerosol challenge. The application proposes that TCR gamma/delta cells function in the systemic immune response to OVA (administered i.p. with Alum) by promoting differentiation of CD4+ TCR alpha/beta cells. These OVA-specific CD4 + cells then promote B-cell differentiation and immunoglobulin class-switching. The visualization and enumeration of these events will suggest possible sites and molecular events whereby TCR gamma/delta cells can affect the immune response. The observations that TCR gamma/delta cells continue to impact on the magnitude of the cellular and humoral response following 2 or 3 immunization or challenges are more perplexing in light of what is known regarding the behavior of memory CD4+ TCR alpha/beta cells and B lymphocytes. This could imply that TCR gamma/delta cells are specific for OVA and that, like TCR alpha/beta B-cells, they exhibit functional memory responses. Alternatively, TCR gamma/delta cells have the same response to OVA upon each exposure, and the functional impact of that response is manifested in the same way irrespective of whether it occurs during the primary or recall response to antigen. These studies represent one of first model systems where all the reagents necessary have been assembled to begin to define the role of TCR gamma/delta cells in a "conventional" immune response. Specifically, they propose to: AIM 1. Determine the impact of TCR gamma/delta cells on commitment of CD4+ TCR alpha/beta cells to the Th2 lineage. AIM 2. Determine the impact of TCR gamma/delta cells in B-cell production of OVA-specific Ig. AIM 3. Determine if TCR gamma/delta T-cells represent innate or adaptive components of the systemic immune response to OVA.