ALCOHOLISM--MODULATION & FUNCTION OF LYMPHOCYTE SUBSETS

我们已经在没有活动性肝病的酗酒者中证明了l）A 活化的CD 8细胞显著增加和2）实质性失衡 在CD 4+、CD 8+和CD 3-CD 19-淋巴细胞的精细亚群中。在一些 没有活动性肝病的酗酒者和许多酒精性肝病患者 疾病时，T细胞的百分比也大幅增加， 是CD 57+。这些和其他结果表明， 细胞免疫系统，研究将提供一个改进的 理解混合免疫抑制和免疫 激活通常存在于酗酒者。 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。表型研究将由 三色和四色流式细胞术方法，特别注意 CD 3 + CD 8（hi）CD 57+、CD 3 + CD 8（hi）CD 57-和CD 3-CD 19-亚群。功能 研究将集中在杀伤活性和调节活性， 通过分选获得全淋巴细胞部分和亚群。 功能研究包括：l）测量新鲜和淋巴因子 自然杀伤细胞和MHC-非限制性T细胞的激活杀伤活性 杀伤细胞; 2）测量杀伤活性及其在 我们最近发现的扩增的CD 3-CD 19-细胞亚组分， 某些酗酒者; 3）MHC限制性T细胞发育的能力 在同种异体驱动系统中的细胞毒性;和4）推定的细胞毒性的能力。 调节性T细胞亚群抑制B细胞增殖和IgG 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。 结果将提供一个详细的图片 外周血细胞毒性/抑制子亚群的差异 正常人、无活动性肝病的酗酒者和 患有肝病的酗酒者。将特别强调 表型和功能属性的变化进展 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.