ALCOHOLISM--MODULATION & FUNCTION OF LYMPHOCYTE SUBSETS

酗酒--调节

• 批准号: 2769147
• 负责人: ROBERT T COOK
• 金额: $ 22万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769147
• 关键词: B lymphocyte; MHC class I antigen; T lymphocyte; alcoholism /alcohol abuse; apoptosis; autoantibody; cell growth regulation; clinical research; ethanol; flow cytometry; human subject; immunopathology; immunosuppression; leukocyte activation /transformation; phenotype; tissue /cell culture

DESCRIPTION: (Adapted from the Investigator's Abstract) Alcoholism and its complications exact a staggering medical cost in the U.S. The increase in infectious diseases is a result of immunodeficiency, and the presence of autoantibodies supports the possibility that autoimmunity may contribute to the organ and tissue damage. Recently, we and others have shown that alcoholics have 1) chronically and markedly activated T-cells, 2) loss or reduction of several lymphocyte subsets, 3) substantial monocyte activation, and 4) functional changes in vitro. Cellular subsets known to be altered phenotypically in alcoholics include CD8+ T-cells, and CD5+ B-cells, and loss of T-cell response to alloantigen in the presence but not in the absence of autologous monocytes. We believe that the loss of subsets and the influence of activated monocytes on the remaining lymphocyte subsets are responsible for much of the immune dysfunction in these patients. The proposal will characterize the mechanisms of subset loss in alcoholics by 1) evaluation of cell-death related marker expression and extent of apoptosis in the activated cell types known to be lost in alcoholics, 2) measurement of the cytokine balance and relative numbers of activated monocytes, 3) analysis of inhibition of T-cell responses to antigen by the activated monocytes, and 4) investigation of the cytokine balance (TH1/TH2) of the remaining lymphocyte subsets in various stages of alcoholism. These evaluations will be carried out on fresh and cultured peripheral blood lymphocytes and monocytes from alcoholic humans under treatment and compared with normal controls. The effect of ethanol will be directly measured on these same functions by the use of short and long-term cell cultures in the presence of carefully controlled continuous ethanol exposures. The methods of analysis are all well-standardized and currently in use in the investigator's laboratory. These include flow cytometry, modifications of several cell-killing assays, and cell proliferation assays. The goal of these investigations is to improve understanding of the significant immunologic changes in chronic alcoholism that underlie the morbidity and death resulting from the increased infectious diseases and organ damage in these patients. This understanding will lie at the heart of initiative for immunotherapy and other interventions designed to reduce the morbidity and mortality in this disease.

描述：（改编自研究者的摘要）酗酒及其 在美国，并发症造成了惊人的医疗费用 传染病是免疫缺陷的结果，并且存在 自身抗体支持自身免疫可能有助于 器官和组织损伤。 最近，我们和其他人已经证明 酗酒者 1) 长期且显着激活的 T 细胞，2) 丧失或 几种淋巴细胞亚群的减少，3) 大量的单核细胞活化， 4) 体外功能变化。 已知发生改变的细胞亚群 酗酒者的表型包括 CD8+ T 细胞和 CD5+ B 细胞，以及 T 细胞对同种抗原的反应丧失，但在存在时不存在 缺乏自体单核细胞。 我们认为子集的丢失和 活化的单核细胞对剩余淋巴细胞亚群的影响是 造成这些患者大部分免疫功能障碍的原因。 这 该提案将通过以下方式描述酗酒者子集丢失的机制：1) 评估细胞死亡相关标志物的表达和细胞凋亡的程度 已知在酗酒者中丢失的活化细胞类型，2) 测量 细胞因子平衡和活化单核细胞的相对数量，3) 活化的 T 细胞对抗原反应的抑制分析 单核细胞，4) 细胞因子平衡 (TH1/TH2) 的研究 酒精中毒各个阶段的剩余淋巴细胞亚群。 这些 将对新鲜和培养的外周血进行评估 来自接受治疗的酗酒者的淋巴细胞和单核细胞并进行比较 与正常控制。 乙醇的影响将直接测量 通过使用短期和长期细胞培养物来实现这些相同的功能 存在仔细控制的连续乙醇暴露。 方法 的分析均经过良好标准化，目前正在使用 调查员的实验室。 这些包括流式细胞术、修饰 多种细胞杀伤测定和细胞增殖测定。 目标是 这些调查是为了提高对重要问题的理解 慢性酒精中毒的免疫学变化是发病率和 传染病和器官损伤增加导致的死亡 这些病人。 这种理解将成为倡议的核心 免疫疗法和其他旨在降低发病率的干预措施 这种疾病的死亡率。