AUTOANTIBODIES TO ACTIVATED LYMPHOCYTES IN SLE

SLE 中活化淋巴细胞的自身抗体

• 批准号: 3155907
• 负责人: JOHN B WINFIELD
• 金额: $ 15.89万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3155907
• 关键词: B lymphocyte; T lymphocyte; antibody specificity; autoantibody; cell population study; human subject; immune complex; immunoregulation; leukocyte activation /transformation; monoclonal antibody; orphan disease /drug; surface antigens; systemic lupus erythematosus; tissue /cell culture

This laboratory has had a long-term interest in study of the nature and significance of anti-lymphocyte autoantibodies in systemic lupus erythematosus (SLE). Very recent investigations utilizing a reverse hemolytic plaque technique have demonstrated increased numbers of endogenously activated T cells (T-PFC), which shed soluble membrane products, in the circulation of patients with active SLE. These T-PFC are strongly correlated with the presence of activated B cells spontaneously secreting immunoglobulin. This suggests that such activated T cells may reflect important immunoregulatory mechanisms. Other data indicate that relatively warm-reactive antibodies of the IgG class exhibit unusual reactivity both with activated T cells and with their soluble products. The over-all objective of this proposal is to further characterize the nature of activated lymphocytes and specifically-reactive antibodies in SLE, and to define their role in the natural history of this disorder. Serial observations in individual patients will provide information concerning the relationship of T-PFC with other immunologic abnormalities and disease expression. SLE antibodies and monoclonal antibodies to resting lumphocytes and to activation neoantigens will be used as probes to identify both the types of T cells which are spontaneously activated and the molecules which are expressed or shed from their surface membranes. The relationship of cell surface neoantigen expression with other nuclear and membrane parameters of cell activation will be examined by flow cytometry. Immune complexes of soluble products of activated T cells and autoantibody will be sought in serum and serum cryoprecipitates. Hybridoma antibodies specific for activated lymphocyte antigens and SLE lymphocyte antigens will be produced.

该实验室长期致力于研究自然界， 抗淋巴细胞自身抗体在系统性狼疮中意义 红斑性狼疮（SLE）。 最近的调查利用了一个反向的 溶血空斑技术已经证明， 内源性活化T细胞（T-PFC），其脱落可溶性膜 产品，在活动性SLE患者的循环中。 这些T-PFC是 与自发激活的B细胞的存在密切相关 分泌免疫球蛋白 这表明这种活化的T细胞可能 反映了重要的免疫调节机制。 其他数据说明 IgG类的相对温反应性抗体表现出不寻常的 与活化的T细胞及其可溶性产物的反应性。 本提案的总体目标是进一步说明 活化淋巴细胞和特异性反应抗体的性质 系统性红斑狼疮，并确定他们的作用，这种疾病的自然史。 个体患者的系列观察将提供信息 关于T-PFC与其他免疫异常的关系 疾病的表达。 SLE抗体和单克隆抗体 静息的淋巴细胞和活化的新抗原将被用作探针， 识别自发激活的T细胞类型， 从细胞膜表面表达或脱落的分子。 细胞表面新抗原表达与其他核抗原表达的关系 和细胞活化的膜参数将通过流式细胞仪检测。 细胞仪 活化T细胞的可溶性产物的免疫复合物和 将在血清和血清冷沉淀物中寻找自身抗体。 杂交瘤 活化淋巴细胞抗原和SLE淋巴细胞特异性抗体 将产生抗原。