ANERGY IN PULMONARY GRANULOMES

我们先前的发现：(1)包括迁移在内的淋巴因子活动 抑制因子、巨噬细胞融合因子与巨噬细胞 从过敏肺中回收趋化因子(MCF) 肉芽肿；(2)静脉注射富含淋巴因子的上清液 抑制非亲缘关系免疫豚鼠迟发性皮肤反应 抗原和(3)瞬时能量和可检测的血清MIF活性 同时出现在肉芽肿形成的初始阶段， 为本申请中提出的研究提供基础。首先，我们将 证实并推广了初步观察，即血清MIF和 皮肤能量存在于肺肉芽肿动物体内，通过 决定了它们显现的时间进程。然后我们将尝试 鉴定和鉴定皮肤致病的可溶性因子 过敏性肺肉芽肿豚鼠的无能反应。要实现 这种被动的无能转移将通过注射血清从 肉芽肿性炎性病变的供体免疫动物 迟发性超敏反应。血清中检测到抑制因子 肉芽肿动物的物理化学特征和他们的 本课程将探讨与循环淋巴因子的关系。被动语态 无能的转移也将通过注射水提取物来尝试。 肺肉芽肿证明抑制因子是直接 在肉芽肿性炎性病变中产生。最后，一次尝试 将对正在分泌的细胞群(S)进行鉴定 参与无能状态的产生和维持的因子(S)。 这些研究将阐明无能的潜在机制。 肉芽肿性炎症及其与无能的可能关系 肺肉芽肿形成的体内调节。

Our previous findings that (1) lymphokine activities including migration inhibitory factor (MIF), macrophage fusion factor (MFF) and macrophage chemotactic factor (MCF) be recovered from hypersensitivity lung granulomas; (2) intravenous administration of lymphokine-rich supernatants inhibits delayed skin reactions in guinea pigs immunized to unrelated antigens and (3) transient energy and detectable serum MIF activity are concurrently present during the initial stage of granuloma formation, provide the basis for studies proposed in this application. First, we will confirm and extend the preliminary observations that serum MIF and cutaneous energy are present in animals with pulmonary granulomas by determining the time course of their manifestation. We will then attempt to identify and characterize soluble factors responsible for cutaneous anergy in guinea pigs with hypersensitivity lung granulomas. To achieve this, passive transfer of anergy will be attempted by injecting serum from donors with granulomatous inflammatory lesions into immune animals with delayed hypersensitivity. Suppressive factors detected in sera of granulomatous animals will be physicochemically characterized and their relationship to circulating lymphokines will be examined. The passive transfer of anergy will also be attempted by injection of aqueous extracts of pulmonary granulomas to demonstrate that suppressive factor is directly produced in the granulomatous inflammatory lesions. Finally, an attempt will be made to identify the cell population(s) which are secreting factor(s) involved in the generation and maintenance of the anergic state. These studies will illuminate the underlying mechanism of anergy in granulomatous inflammation and the possible relationship between anergy and the in vivo regulation of lung granuloma formation.