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：树突状细胞是一种抗原呈递细胞， 在调节适应性免疫中的作用。最近，方法已经成为 可以从各种来源分离这些细胞，包括脐带血， 血液、外周血和骨髓。这引发了人们对 这些细胞的潜在治疗用途。 目标：本提案的主要目标是确定 使用脐带血来源的树突状细胞作为治疗肿瘤的试剂的可行性 预防和治疗早产儿传染病。具体 目的是1）表征新鲜分离和培养衍生的树突状细胞， 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 提呈细胞，以及3）开发自体DC的实用方法 分离、储存和抗原加载。 方法：将树突状细胞 使用免疫磁性分离从脐带血和成人血中获得 技术.新鲜分离和培养的脐带和成人树突状细胞 将比较细胞的谱系标志物的表面表达，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，将评估脐带和成人树突状细胞的 它们的功能能力包括它们诱导幼稚T细胞的能力， 活化和增殖并刺激B细胞成熟为抗体 产生浆细胞。 健康相关性：传染病是一个重大问题， 在新生儿重症监护室住院的极低出生体重（VLBW）婴儿 单位（新生儿重症监护室）。大约25%的极低出生体重新生儿（出生体重 500和1500克）在NICU中至少经历一次记录的 败血症的症状暴露导致住院时间延长 耐药微生物和多种侵入性程序，在存在 免疫不成熟使这些婴儿容易受到医院获得性 感染.树突状细胞可能是理想的免疫载体， 传染源树突状细胞已经显示出呈递细菌和 病毒抗原与T细胞的体外结合。动物研究是令人鼓舞的抗原 脉冲的树突状细胞有效地提供保护性免疫， 水平等于或大于常规佐剂所建立的水平 疫苗。迄今为止，人类研究仅限于I/II期， 在成人志愿者和晚期恶性肿瘤患者中的研究 疾病