B CELL AND T CELL RESPONSES TO POLYSACCHARIDES

B 细胞和 T 细胞对多糖的反应

• 批准号: 3144500
• 负责人: Donna M Ambrosino
• 金额: $ 19.04万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3144500
• 关键词: B lymphocyte; Haemophilus influenzae; T lymphocyte; antibacterial antibody; antibody formation; bacterial antigens; bacterial polysaccharides; cell population study; complement; cytotoxic T lymphocyte; diphtheria toxoid; gene expression; genetically modified animals; helper T lymphocyte; human subject; interferons; interleukin 4; laboratory mouse; leukocyte activation /transformation; lymphokines; mitogens; pertussis toxin; suppressor T lymphocyte; tetanus toxoid; tissue /cell culture

H.influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis are serious pathogens for young children and immunocompromised adults. Predisposing conditions include malignancy, acute and chronic leukemias, Hodgkin's disease, and bone marrow transplant patients. In addition, we have recently described selective immunodeficiencies for these pathogens. The major risk factor for each of these groups of patients is impaired immune response to the capsular polysaccharide (Ps) antigens. Although linking the Ps to proteins (i.e., conjugate vaccines) has greatly improved immunogenicity in older normal children, immunocompromised patients are still at risk. Thus, further understanding of the Ps immune response is of great importance to many patient groups. We propose to study the human in vitro immune response to Ps. We plan to examine the phenotype of B cells responding to Ps, the structural and cellular requirements for Ps activation of B cells, and the role of C3d in Ps activation. Finally, we will study the effect of T cell lymphokines on the Ps activated B cells. To complement the human in vitro work, we plan to study murine Ps responses in vivo. We will focus on the role of T cells and T cell lymphokines on Ps specific responses. Previous studies have had to rely on incomplete and flawed models of T cell depletions. We will employ newly available T cell deficient transgenic mice as well as mice with severe combined immunodeficiency. These murine models will allow us to study the role of specific T cells (CD4, CD8, gamma/delta cells) in the immune response and the ontogeny of response to Ps antigens. Finally, we have developed murine models to evaluate the role of IL-4 and IFN-gamma on antigen specific responses. We will examine the effects of these lymphokines on the subclass specific response to Ps antigens. In summary, we propose to study both in vitro and in vivo B cell and T cell responses to Ps antigens. This work has significance for understanding the impaired responses of many immunocompromised patients. In addition to identifying such patients, new preventive strategies may result from defining the mechanisms involved.

H.influenzae B型（HIB），肺炎链球菌和奈瑟氏菌 脑膜炎是幼儿的严重病原体和免疫功能低下的病原体 成年人。 诱发的条件包括恶性，急性和慢性 白血病，霍奇金病和骨髓移植患者。 在 此外，我们最近描述了这些选择性免疫缺陷 病原体。 这些患者中每个患者的主要危险因素是 对囊囊多糖（PS）抗原的免疫反应受损。 尽管将PS链接到蛋白质（即结合疫苗）的情况很大 改善了年龄较大的正常儿童的免疫原性，免疫功能低下 患者仍处于危险之中。 因此，进一步了解PS免疫 对许多患者群体的反应至关重要。 我们建议研究人类对PS的体外免疫反应。 我们计划 检查B细胞对PS，结构和结构和 PS激活B细胞的细胞需求以及C3D在 PS激活。 最后，我们将研究T细胞淋巴动物对 PS激活的B细胞。 为了补充人类的体外工作，我们计划研究鼠PS的反应 体内。 我们将重点介绍T细胞和T细胞淋巴细胞在PS上的作用 具体响应。 以前的研究必须依靠不完整和 T细胞消耗的有缺陷模型。 我们将采用新的T细胞 不足的转基因小鼠以及严重合并的小鼠 免疫缺陷。 这些鼠模型将使我们能够研究 免疫反应中的特定T细胞（CD4，CD8，γ/Delta细胞）和 对PS抗原的反应的个体发育。 最后，我们开发了鼠 评估IL-4和IFN-GAMMA在抗原特异性方面的作用的模型 回答。 我们将检查这些淋巴细胞对 子类对PS抗原的特异性反应。 总而言之，我们建议研究体外和体内B细胞和T细胞 对PS抗原的反应。 这项工作对于理解 许多免疫功能低下的患者的反应受损。 此外 确定此类患者，可能是由 定义所涉及的机制。