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ROLE OF DENDRITIC CELLS IN CUTANEOUS MALIGNANCY AND AIDS

树突状细胞在皮肤恶性肿瘤和艾滋病中的作用

基本信息

批准号：
3079070
负责人：
DONALD V BELSITO
金额：
$ 7.5万
依托单位：
NEW YORK UNIVERSITY
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

项目摘要

My objective is to test the hypothesis that dendritic cell (DC) abnormalities might (1) be involved in the pathogenesis of multiple cutaneous malignancies in humans and in ultraviolet-B (UVB) induced skin cancers in mice and (2) be at least partially responsible for the immunologic dysfunctions of the Acquired Immunodeficiency Syndrome (AIDS). First, I plan to define the percentage, distribution and phenotypic characteristics of DC (1) in skin of patients with multiple cutaneous malignancies; (2) in the skin and lymph nodes (LN) of mice with UVB-induced cutaneous malignancies and, (3) in the skin, LN and blood of patients with AIDS, with AIDS-related complex (ARC) and with an enhanced risk for developing AIDS. Suitable control groups will be included throughout. Epidermal sheets and cryostat tissue sections of skin and LN will be prepared and stained for a variety of DC surface antigens, including Ia (HLA-DR), using immunoperoxidase techniques. Where appropriate, DC suspensions will be made from skin, LN and blood and analyzed on a FACS 420 cytofluorograph; cytocentrifuge smears will also be prepared and stained as above. The functional status of the DC suspensions from LN and skin of tumor-bearing mice and from LN and blood of patients with AIDS, ARC and an enhanced risk for AIDS will be evaluated in the MLR. This can be done using T cells isolated from LN of these mice and patients and assaying the ability of these T cells to proliferate (thymidine incorporation) and produce interleukin-2. Finally, I shall exmaine the ability of a variety of lymphokines (interleukin-1, interleukin-2 and interferon-Gamma) to modulate any observed effects in cell surface expression and/or antigen-presentation noted in the functional DC studies. I anticipate that these studies will lead to an increased understanding of the biology of DC, especially the inter-relationships among the various DC populations, in normal humans and mice. In addition, these experiments should provide an appreciation of the changes in the percentage, distribution, phenotype and functional properties of DC in patients with cutaneous malignancies, with AIDS, with ARC and with an enhanced risk for AIDS. Finally, data on the potential usefulness of a variety of lymphokines in the treatment of these disorders will be generated.

我的目的是验证树突状细胞（DC）异常可能（1）参与多个人类和紫外线B（UVB）诱导的皮肤恶性肿瘤小鼠的癌症和（2）至少部分负责获得性免疫缺陷综合征（AIDS）的免疫功能障碍。首先，我计划定义百分比，分布和表型多发性皮肤病患者皮肤DC（1）的特征恶性肿瘤;（2）在皮肤和淋巴结（LN）的小鼠与UVB诱导皮肤恶性肿瘤，（3）皮肤，LN和血液中的患者，艾滋病，伴艾滋病相关综合征（ARC），发展艾滋病。将在整个过程中纳入适当的对照组。皮肤和LN的表皮片和低温恒温器组织切片将被制备并染色各种DC表面抗原，包括Ia （HLA-DR），使用免疫过氧化物酶技术。在适当的情况下，DC 悬浮液将由皮肤、LN和血液制成，并在FACS 420上分析细胞荧光照片;细胞离心涂片也将制备并染色，以上 LN和皮肤DC悬液的功能状态荷瘤小鼠和来自LN和AIDS患者的血液，艾滋病风险增加将在MLR中进行评估。这是可以做到使用从这些小鼠和患者的LN中分离的T细胞，这些T细胞增殖的能力（胸苷掺入）和产生白细胞介素-2。最后，我将测试一个品种的能力，淋巴因子（白细胞介素-1、白细胞介素-2和干扰素-γ），调节细胞表面表达中观察到的任何效应和/或在功能性DC研究中注意到的抗原呈递。我预计这些研究将增加对DC生物学的理解，特别是各种DC人群之间的相互关系，正常人和老鼠此外，这些实验应该提供一个评估百分比、分布、表型和皮肤恶性肿瘤患者DC的功能特性，艾滋病，ARC和艾滋病的风险增加。最后，关于各种淋巴因子在治疗这些疾病中的潜在用途将产生紊乱。