ALCOHOLISM--MODULATION & FUNCTION OF LYMPHOCYTE SUBSETS

描述：（改编自研究者摘要）酒精中毒及其 并发症在美国造成了惊人的医疗费用。 传染病是免疫缺陷的结果， 自身抗体支持自身免疫可能有助于 器官和组织损伤 最近，我们和其他人已经表明， 酗酒者有1）慢性和显着激活的T细胞，2）损失或 几种淋巴细胞亚群的减少，3）大量单核细胞活化， （4）体外功能变化。 已知改变的细胞亚群 酗酒者的表型包括CD 8 + T细胞和CD 5 + B细胞， T细胞对同种异体抗原的反应丧失，但在 不存在自体单核细胞。 我们认为，子集的丢失和 活化的单核细胞对其余淋巴细胞亚群的影响是 导致这些患者的免疫功能紊乱。 的 该提案将通过以下方式描述酗酒者亚群丢失的机制：1） 细胞死亡相关标志物表达和细胞凋亡程度的评价 在已知在酗酒者中丢失的活化细胞类型中，2）测量 细胞因子平衡和活化单核细胞的相对数量，3） 分析活化的免疫球蛋白对T细胞对抗原应答的抑制作用 单核细胞，以及4）研究单核细胞的细胞因子平衡（TH 1/TH 2）。 酒精中毒不同阶段的淋巴细胞亚群。 这些 将对新鲜和培养的外周血进行评价 淋巴细胞和单核细胞，并比较 与正常对照。 乙醇的影响将直接测量， 这些相同的功能，通过使用短期和长期的细胞培养， 存在仔细控制的连续乙醇暴露。 的方法 所有分析都是标准化的，目前在 调查员的实验室。 这些包括流式细胞术， 几种细胞杀伤测定和细胞增殖测定。 的目标 这些调查是为了提高对重要的 慢性酒精中毒的免疫学变化是发病的基础， 由于传染病和器官损伤的增加而死亡的人数 这些病人。 这种理解将是主动性的核心， 免疫疗法和其他干预措施，旨在减少发病率和 这种疾病的死亡率。

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.