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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：
3079156
负责人：
DONALD V BELSITO
金额：
$ 7.58万
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 1990-06-30
项目状态：
已结题

项目摘要

The aim of this grant is to test the hypothesis that dendritic cell (DC) abnormalities might (1) be involved in the pathogenesis of ultraviolet-B (UVB) induced skin cancers and (2) be at least partially responsible for the immunologic dysfunctions of the Acquired Immunodeficiency Syndrome (AIDS). I will continue to further define the percentage, distribution and phenotypic characteristics of DC (1) in the skin and lymph modes (LN) of mice and UVB-induced cutaneous malignancies and (2) in the skin and LN of patients with AIDS, with AIDS-related complex (ARC) and with an enhanced risk for developing AIDS. Suitable control groups will be included throughtout. 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 and immunofluorescent techniques. In addition, in situ mRNA hybridization will be used to detect the possibility that DC serve as a reservoir for HIV-1. Where appropriate, DC suspensions will be made from skin and LN 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 will be evaluated in the MLR. This can be done using T cells isolated from LN of these mice and from the blood of patients and assaying the ability of these T cells to proliferate (thymidine incorporation) and produce interleukin-2. The function of in vitro HIV-1-infected DC will also be assessed in the autologous MLR using T cells isolated from the peripheral blood of patients. Finally, the ability of a variety of lymphokines (interleukin-2, interferon-delta, tumor necrosis factor) to modulate any observed defects in cell surface expression and/or antigen-presentation noted in the functional DC studies will be examined. It is anticipated 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.

这笔赠款的目的是检验树突状细胞的假设 (DC) 异常可能 (1) 参与以下疾病的发病机制紫外线 B (UVB) 诱发的皮肤癌，并且 (2) 至少免疫功能障碍的部分原因获得性免疫缺陷综合症（艾滋病）。我会继续进一步定义百分比、分布和表型 DC的特点（1）皮肤和淋巴模式（LN）小鼠和 UVB 诱发的皮肤恶性肿瘤和 (2) 皮肤艾滋病相关综合症 (ARC) 患者的 LN 和 LN 并增加患艾滋病的风险。合适的控制整个过程中将包括小组。表皮片和将制备皮肤和 LN 的低温恒温器组织切片并对多种 DC 表面抗原进行染色，包括 Ia (HLA- DR），使用免疫过氧化物酶和免疫荧光技术。此外，mRNA原位杂交将用于检测 DC 可能是 HIV-1 的储存库。在哪里适当的，直流悬浮液将由皮肤和液氮制成，在 FACS 420 细胞荧光照片上进行分析；细胞离心涂片也将按照上述方法进行准备和染色。功能状态来自荷瘤小鼠的 LN 和皮肤的 DC 悬浮液将在 MLR 中进行评估。这可以使用 T 细胞来完成从这些小鼠的 LN 和患者的血液中分离出来检测这些 T 细胞增殖的能力（胸苷并入）并产生白介素-2。体外功能 HIV-1感染的DC也将在自体MLR中进行评估使用从患者外周血中分离的 T 细胞。最后，多种淋巴因子（白细胞介素2，干扰素-δ、肿瘤坏死因子）来调节任何观察到的细胞表面表达和/或抗原呈递缺陷将检查功能性 DC 研究中提到的内容。这是预计这些研究将导致增加了解 DC 的生物学，特别是间正常人中不同 DC 群体之间的关系和老鼠。此外，这些实验应该提供欣赏百分比、分布的变化， DC患者的表型和功能特性皮肤恶性肿瘤、艾滋病、ARC 和增加患艾滋病的风险。最后，关于潜在用途的数据多种淋巴因子在治疗这些疾病中的作用将被生成。