IMMUNOREGULATORY EFFECTS OF THE INTERFERONS

干扰素的免疫调节作用

• 批准号: 3185240
• 负责人: HOWARD OZER
• 金额: $ 11.42万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-11-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3185240
• 关键词: T lymphocyte; angiography; antibody formation; blood tests; bone marrow exam; cell differentiation; clinical chemistry; density gradient ultracentrifugation; helper T lymphocyte; human subject; human therapy evaluation; immunohematology; immunopharmacology; interferons; interleukin 2; lymphokines; lymphoma; macrophage; monoclonal antibody; monocyte; multiple myeloma; neoplasm /cancer immunotherapy; radioimmunoassay; radiotracer; serology /serodiagnosis; suppressor T lymphocyte

The purpose of this proposal is to define on a molecular, cellular and functional level the mechanisms by which the interferons (IFN) modulate human antibody production in vitro and to test the hypothesis that they may function as immunoregulatory or differentiation-inducing lymphokines in controlling the proliferation of certain B cell malignancies such as nodular lymphoma and hairy cell leukemia. The objectives are: 1) to characterize cellular receptors for interferon expressed by human peripheral blood lymphocyte subsets and malignant cells, 2) to examine the effects of the interferons on phenotypically and functionally define human T cell subsets and 3) to examine the effects of IFN in inducing phenotypic and functional differentiation in vitro of both defined B leukemia/lymphoma cell lines and B malignant populations from patients with nodular lymphoma and hairy cell leukemia. Detection of binding of radioiodinated interferons to human lymphocytes will be used as a probe in the following specific aims: 1) to determine subcellular organelle localization of specific cellular binding sites for the interferons, 2) to monitor cellular uptake of interferon receptors analogous to peptide-hormone receptor mechanisms, 3) to directly determine if the interferons exert their biological functions, including augmentation of antibody production and NK activity in vitro, via receptor mechanisms, and 4) to examine the interrelationship of other lymphokines and interferon receptor expression. From the standpoint of immunoregulation of T cell functions by the interferons, the specific aims are: 1) to examine the effects of the interferons on suppressor and helper T-cell function, defined in a model system involving human primary and polyclonal antibody production in vitro, 2) to study the effect of interferon on phenotypic T cell differentiation, 3) to investigate possible modulation by the interferons of T cell expression of interleukin-2 receptors, and 4) to assess the effects of other lymphokines on interferon-enhanced antibody production in vitro. Finally, the in vitro mechanisms by which IFN (and other lymphokines) might promote differentiation of B cell neoplasms via receptor interactions with normal and/or malignant cellular subsets will be investigated. These studies are thus designed to enhance understanding of the mechanisms involved in interferon modulation of human immune responses and tumor growth in vivo and in vitro.

该建议的目的是在分子，细胞和 功能级 在体外生产人类抗体，并检验了它们可能的假设 在免疫调节或分化诱导淋巴在的功能 控制某些B细胞恶性肿瘤的扩散，例如 结节性淋巴瘤和毛状细胞白血病。 目标是：1） 表征人类表达的干扰素的细胞受体 外周血淋巴细胞亚群和恶性细胞，2）检查 干扰素对表型和功能定义人类的影响 T细胞子集和3）检查IFN在诱导表型中的影响 在体外的功能分化，两种定义的B白血病/淋巴瘤 来自结节淋巴瘤患者的细胞系和B恶性群 和多毛细胞白血病。 检测放射性约束的结合 对人淋巴细胞的干扰素将用作以下 具体目的：1）确定亚细胞细胞器的定位 干扰素的特定细胞结合位点，2）监测细胞 类似于肽激素受体的干扰素受体的摄取 机制，3）直接确定干扰素是否施加 生物学功能，包括增强抗体产生和NK 体外活性，通过受体机制，4）检查 其他淋巴因子和干扰素受体表达的相互关系。 从T细胞功能免疫调节的角度 干扰素，具体目的是：1）检查 在模型中定义的抑制器和辅助T细胞功能的干扰素 在体外涉及人类原代和多克隆抗体的系统， 2）研究干扰素对表型T细胞分化的影响， 3）研究T细胞干扰素可能的调节 白介素2受体的表达，4）评估 其他有关干扰素增强抗体产生的淋巴细胞的体外。 最后，IFN（和其他淋巴细胞）可能的体外机制 通过与受体相互作用与B细胞肿瘤的分化 将研究正常和/或恶性细胞子集。 这些 因此，研究旨在增强对机制的理解 参与人类免疫反应和肿瘤的干扰素调节 体内和体外生长。