ROLE OF DENDRITIC CELLS IN CUTANEOUS MALIGNANCY AND AIDS

这项拨款的目的是检验树突状细胞 (DC)异常可能(1)参与了 中波紫外线(UVB)诱发皮肤癌和(2)至少 对人的免疫功能障碍负有部分责任 获得性免疫缺陷综合症(艾滋病)。我会继续 进一步明确百分比、分布和表型 DC(1)在皮肤和淋巴模式(LN)中的特征 小鼠和UVB诱发的皮肤恶性肿瘤和(2)皮肤 艾滋病患者的LN与艾滋病相关复合体(ARC) 而且患艾滋病的风险也增加了。适当控制 小组将被包括在内。表皮片和 将准备皮肤和LN的冷冻组织切片，并 多种DC表面抗原染色，包括Ia(人类白细胞抗原-1 DR)，使用免疫过氧化物酶和免疫荧光技术。 此外，还将使用原位mRNA杂交法检测 DC可能是HIV-1的宿主。哪里 适当的DC悬浮液将由皮肤和LN和 在FACS420细胞荧光摄影仪上进行分析；细胞离心涂片 也将准备和染色如上。功能状态 荷瘤小鼠层粘连蛋白和皮肤树突状细胞悬液的研究 将在MLR中进行评估。这可以通过使用T细胞来完成 从这些小鼠的LN和患者的血液中分离出来 分析这些T细胞的增殖能力(胸腺嘧啶核苷 掺入)，并产生白介素2。试管苗的功能 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，各种淋巴因子(白介素2， 干扰素-β、肿瘤坏死因子)来调节任何观察到的 细胞表面表达和/或抗原提呈缺陷 在功能DC研究中注明的将被检查。它是 预计这些研究将导致增加 对DC的生物学，特别是对DC的相互作用的了解 在正常人中，不同DC人群之间的关系 还有老鼠。此外，这些实验应该提供一个 赞赏在百分比、分布、 慢性粒细胞白血病患者树突状细胞的表型和功能特性 皮肤恶性肿瘤、艾滋病、ARC和ARC 增加了艾滋病的风险。最后，关于潜在用处的数据 各种淋巴因子在治疗这些疾病中的作用 将会被生成。

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.