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: 6336283
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6336283
• 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，天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，健康个体以及免疫功能低下的人暴露于急性和慢性应激源对自然杀伤（NK）细胞功能有不利影响，并且这种不利的压力效应易于通过认知重建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可用于项目4的研究。此外，还将在未接受干预但处于教育/对照状态的CFS受试者中采集2份样本，间隔12周。管理核心将为项目1和项目4以及实验室核心招募健康、久坐不动的对照，作为正常受试者进行所有试验。拟议的中心将提供一种机制，以促进我们对NK细胞和CFS的理解。将对NK细胞细胞毒性能力的标志物以及肿瘤细胞靶细胞的实际杀伤进行详细比较。可以评估干预对NK细胞功能的影响之间的差异。除了传统的铬释放细胞毒性试验外，项目4还将研究CFS中尚未评价的NK细胞功能状态的重要标志物。这些将包括细胞内穿孔素的流式细胞术测定和通过荧光强度测量测定表面膜粘附分子、L-选择蛋白（CD 62 L）、LFA-1（CD 11 a）和CD 56在NK细胞上的表达程度。这些物质与NK细胞杀死靶细胞和/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相关。这些标志物与CFS相关的低NK细胞活性的关系，急性和慢性应激对NK细胞功能的影响，或通过行为干预对生活应激的调节，以前没有研究过。我们将研究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对NK细胞细胞毒性、细胞内穿孔素水平和表面标志物的影响。所有这些研究将在2个CFS组受试者中进行干预前/干预后，并在健康久坐对照组中进行一次。该设计将允许确定CFS和健康对照之间的差异，以及通过比较干预前后相对于CFS对照受试者的结果来确定行为干预的影响。