HUMAN LYMPHOCYTE ACTIVATION--ROLE OF DENDRITIC CELLS

树突状细胞是白细胞的一种微量亚群。当抗原在树突状细胞上呈递给免疫系统时，会引起强烈的免疫反应。已经开发出从人体血液、发炎关节和皮肤中分离树突状细胞的方法。我们使用树突状细胞来研究移植、关节炎、牛皮癣以及对肿瘤和传染病（流感、艾滋病）的抵抗中的免疫反应的不同方面。我们的目标包括：a)开发针对树突状细胞表面和细胞内成分的单克隆抗体和DNA探针。b)概述由血液和病变组织中的树突状细胞产生的炎症细胞因子和细胞因子受体的范围。c)克隆可能介导类风湿性关节炎和牛皮癣的自身反应性，以及肿瘤、流感和艾滋病的保护性免疫的T细胞。d)研究暴露于艾滋病病毒（HIV-1）的树突状细胞对CD4+ T细胞的细胞病变感染的传播。比较从血液、皮肤和炎症部位分离的树突状细胞。测试不同类型的免疫T细胞和抗hiv抗体对这种传播的影响。产生CD4和CD8亚群的hiv特异性免疫T细胞。评估免疫T细胞对hiv感染单核细胞的作用。e)开发从未成熟祖细胞中产生大量树突状细胞的方法，并利用这些方法将肿瘤和感染因子（流感、HIV-1）的抗原呈递给人类T细胞。f)评估树突状细胞向T细胞呈递超抗原的机制，包括尝试识别自身免疫性疾病中树突状细胞可能携带的超抗原。g)评估人类同种异体骨髓嵌合体中树突状细胞植入的个体发生和动力学，树突状细胞在免疫重建中的作用，以及树突状细胞祖细胞的鉴定和支持其生长的条件。h)利用树突状细胞产生针对病毒、肿瘤和自身抗原的抗原特异性细胞溶解T淋巴细胞（ctl）。

Dendritic cells are a trace subpopulation of white blood cells. When antigens are presented on dendritic cells to the immune system, strong immune responses are induced. Methods have been developed to isolate dendritic cells from human blood, inflamed joints and skin. We use dendritic cells to study different aspects of the immune response in transplantation, arthritis, psoriasis, and resistance to tumors and infectious disease (influenza, AIDS). Our aims include: a) Develop monoclonal antibodies and DNA probes to cell surface and intracellular constituents of dendritic cells. b) Outline the range of inflammatory cytokines and cytokine receptors that are made by dendritic cells from blood and from diseased tissues. c) Clone T cells that may mediate autoreactivity in rheumatoid arthritis and psoriasis, and protective immunity in tumors, influenza, and AIDS. d) Study the transmission of a cytopathic infection with the AIDS virus from dendritic cells that have been exposed to the virus (HIV-1) to CD4+ T cells. Compare dendritic cells isolated from blood, skin, and inflammatory sites. Test the effect of different types of immune T cells and anti-HIV antibodies on this transmission. Generate HIV-specific immune T cells of both CD4 and CD8 subsets. Evaluate the effects of immune T cells on HIV-infected monocytes. e) Develop methods for generating large numbers of dendritic cells from immature progenitors, and use these to present antigens from tumors and infectious agents (influenza, HIV-1) to human T cells. f) Evaluate mechanisms whereby dendritic cells present superantigens to T cells, including attempts to identify superantigens that may be carried by dendritic cells in autoimmune disease. g) Evaluate in human allogeneic bone marrow chimeras the ontogeny and kinetics of dendritic cell engraftment, the role of dendritic cells in immune reconstitution, and the identification of dendritic cell progenitors and conditions supporting their growth. h) Use dendritic cells to generate antigen-specific cytolytic T lymphocytes (CTLs) to viral, tumor, and auto antigens.