DENDRITIC CELL IMMUNIZATION OF PRETERM NEONATES

早产儿的树突状细胞免疫

• 批准号: 6656332
• 负责人: KURT R SCHIBLER
• 金额: $ 7.4万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6656332
• 关键词: T lymphocyte; antigen presenting cell; autologous transplantation; biomarker; cell adhesion molecules; cell component structure /function; cell proliferation; communicable disease control; cord blood; cryopreservation; cytokine receptors; dendritic cells; enzyme linked immunosorbent assay; flow cytometry; histocompatibility; human subject; iatrogenic disease; immunization; immunomagnetic separation; leukocyte activation /transformation; method development; newborn human (0-6 weeks); premature infant human; tissue /cell culture

DESCRIPTION: (Provided by Applicant) Background: Dendritic cells are antigen presenting cells that play a critical role in regulation of adaptive immunity. Recently, methods have become available to isolate these cells from a variety of sources including cord blood, peripheral blood, and bone marrow. This has sparked interest in potential therapeutic use of these cells. Objectives: The primary objective of this proposal is to determine the feasibility of using cord blood derived dendritic cells as agents for prevention and treatment of infectious diseases in preterm infants. Specific aims are 1) to characterize freshly isolated and culture-derived dendritic cells generated from umbilical cord blood and adult peripheral blood, 2) to evaluate the functional capabilities of neonatal dendritic cell as antigen presenting cells, and 3) to develop practical methods for autologous DC isolation, storage, and antigen loading. Methods: Dendritic cells will be obtained from cord blood and adult blood using immunomagnetic separation techniques. Freshly isolated and culture-derived cord and adult dendritic cells will be compared for surface expression of lineage markers, major histocompatibility molecules, adhesion molecules, co-stimulatory molecules and cytokine receptors. Also, cord and adult dendritic cells will be evaluated for their functional capabilities including their ability to induce naive T cell activation and proliferation and to stimulate B cell maturation into antibody producing plasma cells. Health Relatedness: Infectious diseases represent a significant problem for very low birth weight (VLBW) infants hospitalized in Newborn Intensive Care Units (NICU). Approximately 25 percent of VLBW neonates (birth weight between 500 and 1500 grams) in the NICU experience at least one documented episode of sepsis during their hospital course. Prolonged hospitalization with exposure to resistant organisms and multiple invasive procedures, in the presence of immunologic immaturity renders these infants vulnerable to hospital-acquired infections. Dendritic cells may be ideal vehicles for immunization against infectious agents. Dendritic cells have been shown to present bacterial and viral antigens to T cells in vitro. Animal studies are encouraging as antigen pulsed dendritic cells are efficacious in providing protective immunity at a level equal to or greater than that established by conventional adjuvant vaccines. To date, studies in humans have been limited phase I/II to investigations in adult volunteers and in patients with advanced malignant diseases.

描述：（申请人提供） 背景：树突状细胞是抗原呈递细胞，可发挥关键 在适应性免疫调节中的作用。最近，方法已经成为 可用于将这些单元与包括绳索在内的各种来源分离 血液，外周血和骨髓。这引起了人们的兴趣 这些细胞的潜在治疗使用。 目标：该提案的主要目的是确定 使用绳索血液衍生的树突状细胞作为代理的可行性 预防和治疗早产儿的传染病。具体的 目的是1）表征新鲜孤立和培养的树突状 由脐带血和成人外周血产生的细胞，2） 评估新生儿树突状细胞作为抗原的功能能力 呈现细胞，3）开发自体DC的实用方法 隔离，存储和抗原负荷。 方法：树突状细胞将是 通过免疫磁分离从脐带血和成人血液中获得 技术。新鲜隔离和培养的绳索和成年树突状 将比较细胞的谱系标记表面表达，主要 组织相容性分子，粘附分子，共刺激分子和 细胞因子受体。此外，将评估绳索和成年树突细胞 它们的功能功能，包括诱导幼稚T细胞的能力 激活和增殖并刺激B细胞成熟到抗体中 产生浆细胞。 健康相关性：传染病是一个重大问题 在新生儿重症监护病房住院的婴儿出生体重（VLBW）非常低（VLBW） 单位（NICU）。 VLBW新生儿大约25％ 500和1500克）在NICU体验中至少有一个记录的一集 败血症在他们的医院课程中。长时间住院和暴露 在存在的情况下 免疫学不成熟会使这些婴儿很容易受到医院的影响 感染。树突状细胞可能是用于免疫的理想车辆 感染者。已经显示树突状细胞呈现细菌和 在体外对T细胞的病毒抗原。动物研究令人鼓舞 脉冲的树突状细胞有效地提供保护性免疫 等于或大于常规佐剂建立的水平 疫苗。迄今为止，人类的研究一直是I/II期有限的 对成人志愿者和晚期恶性患者进行调查 疾病。