IMMUNOREGULATORY EFFECTS OF THE INTERFERONS

这项提案的目的是定义一种分子、细胞和 功能水平干扰素的调节机制 在体外产生人类抗体，并检验它们可能 发挥免疫调节或诱导分化淋巴因子的作用 控制某些B细胞恶性肿瘤的增殖，如 结节性淋巴瘤和毛细胞白血病。目标是：1) 人表达干扰素细胞受体的鉴定 外周血淋巴细胞亚群和恶性细胞，2)检测 干扰素对人类表型和功能的影响 T细胞亚群和3)检测干扰素诱导表型的作用 明确的B白血病/淋巴瘤的体外功能分化 结节性淋巴瘤患者的细胞系和B恶性群体 和毛细胞白血病。放射性碘结合的检测 干扰素对人淋巴细胞的作用将在以下方面用作探针 具体目标：1)确定细胞内细胞器的定位 干扰素的特定细胞结合部位，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发挥其作用 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，以及4)检查 其他淋巴因子与干扰素受体表达的相互关系。 从免疫调节T细胞功能的角度看 干扰素的具体目标是：1)检查 干扰素对抑制和辅助T细胞功能的影响，在模型中定义 涉及体外生产人类初级和多克隆抗体的系统， 2)研究干扰素对T细胞表型分化的影响。 3)研究T细胞干扰素可能的调节作用 白介素2受体的表达，以及4)评估 其他淋巴因子对干扰素增强体外抗体产生的影响。 最后，干扰素(和其他淋巴因子)的体外机制 通过与受体相互作用促进B细胞肿瘤的分化 将对正常和/或恶性细胞亚群进行调查。这些 因此，研究旨在加强对这些机制的理解。 干扰素对人体免疫反应和肿瘤的调节作用 体内生长和体外生长。

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.