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CHARACTERIZATION OF THE IMMUNOREGULATORY CIRCUITS IN MAN

人类免疫调节回路的特征

基本信息

批准号：
3152911
负责人：
Chikao Morimoto
金额：
$ 10.5万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1988-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152911
关键词：
Sjogren's syndrome autoimmune disorder cell cell interaction clone cells helper T lymphocyte human subject immunodeficiency immunopathology immunoregulation immunotherapy juvenile rheumatoid arthritis membrane activity monoclonal antibody suppressor T lymphocyte systemic lupus erythematosus

项目摘要

Recent studies demonstrate that human T cell pool is heterogeneous with respect to cell surface markers and functional programs. Moreover, the cells which comprise the regulatory circuits controlling help and suppression are still poorly defined despite their importance in a host of human diseases, including autoimmune and immunodeficiency disorders. We believe, given the major recent technical breakthroughs in the definition of cell surface markers, functional assay systems, and cloning techniques, that one can develop important new insights into the immunoregulatory circuit in man. Furthermore, we have just developed a new set of monoclonal antibodies which define the T4 suppressor inducer subset (anti-2H4 antibody) and the T4 helper inducer subset (anti-4B4 antibody) that will help in the resolution of the heterogeneity of T4 cells. To characterize the immunoregulatory circuit in man, we plan to take advantage of the recently developed primary in vitro anti-DNP antibody forming system. This system allows for a precise examination of cell-cell interactions involved in the generation of supression of anti-DNP antibody production and for the characterization of the factors released by immunoregulatory T cells. Furthermore, we plan to develop KLH specific T cell clones which have unique regulatory activities. In addiiton, we plan to analyze the T cell subsets, functions of isolated cells, and fine specificity of naturally occurring anti-T cell antibodies in patients with systemic lupus erythematosus, juvenile rheumatoid arthritis, and Sjogren's disease. We believe that the analysis of both normal cells and cells from patients with autoimmune disease will provide new insights into the heterogeneity of the diseases and the complexity of the immunoregulatory circuit. It is hoped that a better understanding of the regulatory circuits in man will be critical for both an understanding of the basic biology of the human lymphocytes and for an understanding of disorders of lymphocytes which are present in a host of human diseases. Lastly, it is believed that rational therapy depends on the precise understanding of the immunoregulatory circuit.

最近的研究表明，人类T细胞库是异质的，关于细胞表面标记和功能程序。而且包括控制辅助的调节电路的单元，尽管抑制在许多领域很重要，人类疾病，包括自身免疫和免疫缺陷病症。我们我相信，鉴于最近在定义上的重大技术突破，细胞表面标记、功能分析系统和克隆技术，人们可以对免疫调节机制有新的认识，此外，我们刚刚开发了一套新的定义T4抑制诱导子亚群的单克隆抗体（抗2 H4抗体）和T4辅助诱导物亚群（抗4 B4抗体）这将有助于解决T4细胞的异质性。到描述人类免疫调节回路的特征，我们计划利用最近开发的主要体外抗DNP抗体形成系统该系统允许对细胞-细胞参与抗DNP抗体抑制产生的相互作用生产和表征的因素释放免疫调节T细胞。此外，我们计划开发KLH特异性T 具有独特调节活性的细胞克隆。此外，我们计划分析T细胞亚群、分离细胞的功能，特异性天然存在的抗T细胞抗体在患者系统性红斑狼疮、幼年类风湿性关节炎和干燥综合征疾病我们相信，对正常细胞和来自自身免疫性疾病患者将提供新的见解，疾病的异质性和免疫调节的复杂性电路. 希望能更好地了解监管人体内的神经回路对于理解人类淋巴细胞的生物学，并了解淋巴细胞，其存在于人类疾病的宿主中。最后是他认为，合理的治疗取决于对疾病的准确理解。免疫调节回路