Platelet Contribution to Thymus-dependent B cell Immunity

血小板对胸腺依赖性 B 细胞免疫的贡献

• 批准号: 7103142
• 负责人: BENNETT David ELZEY
• 金额: $ 11.06万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-15 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7103142
• 关键词: B lymphocyte; CD antigens; CD40 molecule; T lymphocyte; glycoproteins; humoral immunity; immunoregulation; laboratory mouse; leukocyte activation /transformation; platelet activation; platelets; protein binding; B lymphocyte; CD antigens; CD40 molecule; T lymphocyte; glycoproteins; humoral immunity; immunoregulation; laboratory mouse; leukocyte activation /transformation; platelet activation; platelets; protein binding

DESCRIPTION (provided by applicant): Platelets are abundant, anucleated cells that mediate multiple functions, the most readily recognized of which is coagulation and hemostasis. It is now clear that activated platelets modulate local inflammatory responses including contact sensitivity, inflammatory bowel disease, and atherosclerosis through the interaction of platelet-derived ligands with endothelial cells and infiltrating leukocytes. Also, platelets express CD40L (CD154), which is an important ligand for modulating adaptive immunity. To determine whether platelet-derived CD40L also modulated adaptive immunity, studies were initiated to characterize the effect of CD40L on T and B cell responses. A clear understanding of the platelet-derived signals necessary for optimal induction of adaptive immunity is important to understanding early events in immune activation. Data recently reported by our group demonstrate that platelet-derived CD40L is important for the development of adaptive immunity. The data demonstrate that activated platelets induce dendritic cell maturation and B cell isotype switching, and enhance CD8+ T cell responses. Importantly, platelet-derived CD40L alone was sufficient for the induction of isotype switching by B cells and augmentation of T lymphocyte antiviral responses. Furthermore, normal mice depleted of platelets prior to adenovirus injection exhibit decreased production of adenovirus-specific IgG, and platelets were shown to be necessary for enhanced B cell germinal center formation, underscoring the importance of platelets in the generation of an optimal adaptive immune response. We hypothesize that platelet-derived CD40L is an early signal from the innate immune compartment that is necessary for optimal development of adaptive immunity. To test the hypothesis, studies are outlined to assess the effect of platelet-derived CD40L on B cell activation and antibody production. LAY STATEMENT Several diseases including atherosclerosis, inflammatory bowel disease, and diabetes are believed to arise from improperly regulated inflammatory immune responses, of which platelets may play a significant role. Identifying and characterizing mechanisms of platelet modulation of the immune response will aid in treatment strategies for combating these clinical situations.

描述（由申请人提供）： 血小板是丰富的，核酸的细胞，介导多种功能，最容易认识到的是凝血和止血。现在很明显，活化的血小板通过血小板衍生的配体与内皮细胞和浸润的白细胞的相互作用调节局部炎症反应，包括接触敏感性，炎症性肠病和动脉粥样硬化。同样，血小板表达CD40L（CD154），这是调节适应性免疫的重要配体。为了确定血小板来源的CD40L是否还调节适应性免疫，开始研究CD40L对T和B细胞反应的影响。对最佳诱导适应性免疫所需的血小板衍生信号的清晰理解对于理解免疫激活中的早期事件很重要。我们小组最近报道的数据表明，血小板来源的CD40L对于自适应免疫的发展很重要。数据表明，活化的血小板会诱导树突状细胞成熟和B细胞同种型切换，并增强CD8+ T细胞反应。重要的是，仅血小板衍生的CD40L足以通过B细胞诱导同种型切换和T淋巴细胞抗病毒反应的增强。此外，在注射腺病毒之前耗尽血小板的正常小鼠表现出降低的腺病毒特异性IgG产生，而血小板被证明是增强B细胞生发中心形成所必需的，强调了血小板在最佳自适应免疫反应中的产生中的重要性。我们假设血小板衍生的CD40L是先天免疫室的早期信号，这是最佳发展适应性免疫所必需的。为了检验该假设，概述了研究以评估血小板衍生的CD40L对B细胞激活和抗体产生的影响。 外行陈述了几种疾病，包括动脉粥样硬化，炎症性肠病和糖尿病是由于调节不当的炎症免疫反应引起的，血小板可能起重要作用。识别和表征免疫反应的血小板调节机制，将有助于制定对抗这些临床情况的治疗策略。