ALCOHOLISM--MODULATION & FUNCTION OF LYMPHOCYTE SUBSETS

我们已经在无活动性肝病的酗酒者中进行了演示)A)L 活化的CD8细胞显著增加，2)严重失衡 CD_4~+、CD_8~+和CD_3~-CD19~-淋巴细胞亚群。在一些 无活动性肝病的酗酒者和许多有酒精性肝病的人 在疾病方面，T细胞的百分比也有大幅增加 均为CD57+。这些和其他结果表明了一种广泛的精神错乱 对细胞免疫系统的研究将提供一种改进的 理解混合免疫抑制和免疫的框架 在酗酒者中普遍存在的激活。 我们建议对酗酒者的外周血淋巴细胞进行表征。 通过表型和功能研究。表型研究将在 三色和四色流式细胞术，特别注意 CD3+CD8(Hi)CD57+、CD3+CD8(Hi)CD57-和CD3-CD19-亚群。功能性 研究将集中在杀戮活动和调节活动上。 通过分选获得全淋巴细胞分数和亚群。 功能研究包括：L)新鲜和淋巴因子的测定 自然杀伤细胞和MHC-非限制性T细胞激活的杀伤活性 杀伤细胞；2)杀伤活性的测定及其增强 我们最近发现的扩展的CD3-CD19-细胞亚组分 部分酗酒者；3)MHC限制性T细胞发育能力 同种异体驱动系统的细胞毒性；以及4)假定的 调节性T细胞亚群抑制B细胞增殖和免疫球蛋白 体外生产。 这些措施将在酗酒者群体之间进行详细比较 有和没有活动性肝病的人，以及正常和 疾病控制中心。调查结果将提供有关 外周血细胞毒/抑制亚群的差异 正常人、无活动性肝病的酒精者和 患有肝病的酗酒者。将特别强调 细胞表型和功能属性变化的研究进展 酒精性肝不同阶段相关淋巴细胞亚群的变化 疾病。

We have demonstrated in alcoholics without active liver disease l) A significant increase in activated CD8 cells and 2) substantial imbalance in the fine subsets of CD4+, CD8+ and CD3- CD19-lymphocytes. In some alcoholics without active liver disease and in many with alcoholic liver disease, there is also a substantial increase in the percentage of T-cells which are CD57+. These and other results indicate a widespread derangement of the cellular immune system, study of which will provide an improved framework for understanding the mixed immune suppression and immune activation commonly present in alcoholics. We propose to characterize the peripheral blood lymphocytes of alcoholics by phenotype and by functional studies. Phenotypic studies will be by three and four-color flow cytometric methods, with special attention to CD3+CD8(hi)CD57+, CD3+CD8(hi)CD57- and CD3-CD19- subsets. Functional studies will focus on the killing activity and the regulatory activity of both whole lymphocyte fraction and subsets obtained by sorting. Functional studies include: l) measurement of fresh and lymphokine activated killing activity by natural killer and MHC-non-restricted T killer cells; 2) measurement of killing activity and its augmentation in the expanded CD3-CD19- cell subfractions we have recently discovered in some alcoholics; 3) the capacity for development of MHC-restricted T-cell cytotoxicity in an allo driven system; and 4) the ability of putative regulatory T-cell subsets to inhibit B-cell proliferation and IgG production in vitro. These measures will be compared in detail between groups of alcoholics with and those without active liver disease, and with both normal and disease controls. The results will provide a detailed picture of the differences in the cytotoxic/suppressor subsets of peripheral blood lymphocytes between normals, alcoholics without active liver disease, and alcoholics with liver disease. There will be special emphasis on the progression of changes in the phenotypic and functional attributes of the relevant lymphocyte subsets during the different stages of alcoholic liver disease.