TCR CELLS PROMOTE TH2 LINEAGE COMMITMENT AND IGE PRODUC

描述（改编自研究者摘要）：总体目标 这个项目是确定TCR γ/δ细胞的细胞界面， 参与对模型蛋白抗原的全身免疫应答， 卵清蛋白（OVA）。他们有惊人的结果，TCR γ/δ细胞是 T-和B-细胞系统免疫应答的有效贡献者， 我们的研究使用的是哮喘小鼠模型。卵清蛋白激发的野生型小鼠 表现出明显的过敏性炎症反应，通过气道 嗜酸性粒细胞增多和血清IgE升高。这些反应在TCR中减弱 γ-/-动物中，并且在TCR β-/-小鼠中完全不存在。气道 对雾化乙酰甲胆碱的反应性也降低， 动物相对于攻击的野生型小鼠。这对于缺乏TCR的小鼠是正确的 γ/δ细胞，或在耗尽TCR的野生型小鼠中 仅在对气雾剂激发的回忆反应期间使用γ/δ细胞。的 本申请提出TCR γ/δ细胞在全身免疫中起作用 通过促进细胞分化对OVA（用明矾腹膜内给药）的反应， CD 4 + TCR α/β细胞。这些OVA特异性CD 4+细胞然后促进B细胞增殖。 分化和免疫球蛋白类别转换。可视化和 这些事件的计数将提示可能的位点和分子事件 由此TCR γ/δ细胞可以影响免疫应答。的意见 TCR γ/δ细胞继续影响细胞免疫的大小， 2或3次免疫或攻毒后的体液反应 根据已知的关于记忆性CD 4 + TCR的行为， α/β细胞和B淋巴细胞。这可能意味着TCR γ/δ细胞 是特异性的卵清蛋白和，像TCR α/β B细胞，他们表现出 功能性记忆反应或者，TCR γ/δ细胞具有相同的免疫原性。 每次暴露后对OVA的反应，以及该反应的功能影响 无论它是否发生在 对抗原的初次或回忆反应。这些研究代表了 模型系统，其中所有必要的试剂已经组装好，开始 定义TCR γ/δ细胞在“常规”免疫应答中的作用。 具体而言，他们建议：目标1。确定TCR γ/δ的影响 细胞对CD 4 + TCR α/β细胞向Th 2谱系定型的影响。AIM 2. 确定TCR γ/δ细胞在B细胞产生中的影响， OVA特异性IG。AIM 3.确定TCR γ/δ T细胞是否代表先天性 或对OVA的系统性免疫应答的适应性成分。

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.