EFFECT OF STRESS AND CBSM ON NATURAL KILLER CELL ACTIVITY IN CFS

压力和 CBSM 对 CFS 自然杀伤细胞活性的影响

• 批准号: 6256263
• 负责人: Mary A Fletcher
• 金额: $ 5.01万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6256263
• 关键词: CD antigens; behavioral /social science research tag; cell mediated lymphocytolysis test; chronic fatigue syndrome; clinical research; cognitive behavior therapy; cooperative study; cortisol; cytolysins; epinephrine; flow cytometry; human subject; leukocyte activation /transformation; natural killer cells; norepinephrine; pore forming protein; psychological stressor; psychoneuroimmunology; selectins; tumor necrosis factor alpha

Natural cell mediated immunity is frequently decreased in individuals who meet the case definition of chronic fatigue syndrome (CFS). Our research group and others have noted that exposures of healthy individuals as well as immunocompromised persons to acute and chronic stressors have an adverse effect on natural killer (NK) cell function, and that this adverse stress effect is susceptible to amelioration by behavioral interventions in which cognitive restructuring and relaxation training are taught. In this Multidisciplinary Research Center, Project 2 will carry out such an intervention for individuals who meet the diagnosis criteria for CFS. The intervention will be carried out over a 12 week period. Blood samples from both pre-intervention and post-intervention will be available for study in Project 4. Also available will be 2 samples collected 12 weeks apart on CFS subjects who do not receive the intervention, but are in an education/control condition. The Administrative Core will enroll healthy, sedentary controls for both Project l and Project 4 and for the Laboratory Core as normal subjects for all assays being done. The proposed Center will provide a mechanism to advance our understanding of NK cells and CFS. A detailed comparison will be made of markers of NK cell cytotoxic capacity as well as actual killing of tumor cell target cells. The differences between effect of the intervention on NK cell function can be evaluated. In addition to the traditional chromium release cytotoxicity assay, Project 4 will look at important markers of NK cell functional status not yet evaluated in CFS. These will include flow cytometric determination of intracellular perforin and determination of degree of expression on NK cells of the surface membrane adhesion molecules, L-selectin (CD62L), LFA-1 (CDlla) and CD56 by fluorescence intensity measurements. These substances are associated with the ability of NK cells to-kill target cells and/or to interact with vascular epithelial cells and pass from peripheral circulation into tissue. The relationship of these markers to the low NK cell activity associated with CFS, to effects of acute and chronic stress on NK cell function or to the modulation of life stress by behavioral interventions has not previously been studied. We will examine the effects on NK cell cytotoxicity, intracellular perforin levels and surface markers of in vitro exposure of peripheral blood cells to stress hormones (epinephrine, norepinephrine, cortisol) and tumor necrosis factor-o:. All of these studies will be done pre/post intervention in the 2 CFS groups of subjects and one time in the healthy, sedentary controls. This design will allow the determination of differences between CFS and healthy controls as well as the impact of the behavioral intervention by comparing findings before and following the intervention relative to CFS control subjects.

在符合慢性疲劳综合征(CFS)病例定义的个体中，自然细胞介导的免疫力经常降低。我们的研究小组和其他人已经注意到，健康的人以及免疫功能低下的人暴露在急性和慢性应激源下会对自然杀伤(NK)细胞功能产生不利影响，这种不利的应激影响很容易通过教授认知结构调整和放松训练的行为干预来改善。在这个多学科研究中心，项目2将对符合CFS诊断标准的个人进行这样的干预。干预将在12周内进行。干预前和干预后的血液样本将在项目4中用于研究。还将提供两个相隔12周从未接受干预但处于教育/控制状况的CFS受试者身上采集的样本。管理核心将为L项目和项目4以及实验室核心登记健康的、久坐的对照，作为所有正在进行的分析的正常对象。拟议的中心将提供一个机制，以促进我们对NK细胞和CFS的了解。将对NK细胞杀伤能力的标志物以及对肿瘤细胞靶细胞的实际杀伤能力进行详细比较。不同干预措施对NK细胞功能的影响程度不同。除了传统的铬释放细胞毒性试验外，项目4还将着眼于尚未在CFS中评估的NK细胞功能状态的重要标记物。其中包括流式细胞术检测细胞内穿孔素，以及用荧光强度法检测NK细胞表面膜黏附分子L-选择素(CD62L)、LFA-1(CD11a)和CD56的表达程度。这些物质与NK细胞杀伤靶细胞和/或与血管上皮细胞相互作用并从外周循环进入组织的能力有关。这些标记物与CFS相关的低NK细胞活性、急、慢性应激对NK细胞功能的影响或行为干预对生活应激的调节之间的关系尚未被研究过。我们将检测外周血细胞体外暴露于应激激素(肾上腺素、去甲肾上腺素、皮质醇)和肿瘤坏死因子-O：时对NK细胞毒性、细胞内穿孔素水平和表面标志的影响。所有这些研究都将在两组CFS受试者的干预前/干预后进行，并在健康的久坐对照组中进行一次。这一设计将允许确定CFS和健康对照之间的差异以及行为干预的影响，方法是将干预前和干预后的结果与CFS对照对象进行比较。