IMMUNOBIOLOGY OF KAPOSIS SARCOMA TUMOR CELLS

牛皮癣是一种常见的皮肤病，个人感染 艾滋病病毒的发展，虽然卡波西肉瘤（KS）仍然作为 皮肤识别和诊断年轻人艾滋病的标志 患者这个提议的基础是围绕我们的小说 观察，一种特殊类型的皮肤相关的巨噬细胞称为 真皮树突状细胞，在艾滋病患者中急剧增加， 牛皮癣和KS，以及另一种艾滋病相关的皮肤病， 环状肉芽肿（GA）。在艾滋病流行之前， 银屑病，KS和GA之间的明显联系，它们的相对选择性 我们观察到艾滋病患者增加， 艾滋病患者和非艾滋病患者，他们都有一个共同的细胞特征， 也就是真皮树突细胞这一发现有力地表明了 病理生理作用的真皮树突状细胞，并在这一建议，我们 将评估真皮树突状细胞在艾滋病背景下的作用 感染，以及在特发性，或非艾滋病相关，银屑病 患者这项提案的主旨是确定皮肤 皮肤中的树突状细胞可以被HIV激活， 激活，这是如何转化为产生一个无序的 皮肤细胞因子网络（包括白细胞介素-1，IL- 1，粒细胞- 单核细胞集落刺激因子，GM-CSF，肿瘤坏死因子， TNF-α和碱性成纤维细胞生长因子（bFGF），最终 负责组织学特征，包括血管生成、表皮 角质形成细胞过度增殖和T细胞浸润。本研究将 让我们清楚地了解到我们目前 假定在艾滋病相关银屑病中具有重要意义，即： HIV -> T细胞->淋巴因子->真皮树突状细胞-> IL-1，GM-CSF， TNF-α，bFGF ->牛皮癣。我们的实验方法包括： 组织切片中真皮树突状细胞的相关性鉴定 皮肤树突状细胞的分离和鉴定 在体外;检查真皮树突细胞如何影响其他土著 体外和体内实验中皮肤的细胞类型; HIV和真皮树突细胞之间相互作用的表征。 在这些实验中使用的技术包括：细胞培养;分化培养。 离心;免疫组织化学染色，体外巨噬细胞和 淋巴细胞功能研究;生物测定和北方印迹分析动物 艾滋病毒/皮肤感染的研究和各种分子生物学研究 树突细胞相互作用我们将研究活化真皮的作用， 树突状细胞在兔皮肤银屑病样改变中的作用。这些模型 系统，连同描述性的体外结果， 推进我们对复杂的免疫调节功能障碍的理解 与艾滋病有关的皮肤病的特征，如牛皮癣。这种新 知识将导致针对艾滋病毒激活的治疗策略 真皮树突状细胞，以及随之而来的细胞因子网络的紊乱， 治疗艾滋病患者的KS和银屑病。

Psoriasis is one of the common skin diseases that individuals infected with the AIDS virus develop, although Kaposi's sarcoma (KS) remains as the hallmark for the cutaneous recognition and diagnosis of AIDS in young patients. The basis for this proposal is centered around our novel observation, that a specific type of skin-related macrophage called the dermal dendrocyte, is dramatically increased in AIDS patients with psoriasis and KS, as well as in another AIDS related skin disease, granuloma annulare (GA). While prior to the AIDS epidemic there was no apparent link between psoriasis, KS and GA, their relatively selective increase in AIDS patients can be understood by our observation that in both AIDS and non-AIDS patients, they all share a common cellular denominator, which is the dermal dendrocyte. This discovery strongly suggests a key pathophysiological role for the dermal dendrocyte, and in this proposal we will evaluate the role of the dermal dendrocyte in the context of HIV infection, as well as in idiopathic, or non-AIDS-related, psoriasis patients. The thrust of this proposal is to determine how dermal dendrocytes in skin can be targeted for activation by HIV, and once activated, how this becomes translated into producing a disordered cutaneous cytokine network (involving interleukin- 1, IL- 1, granulocyte- monocyte colony stimulating factor, GM-CSF, tumor necrosis factor, TNF-alpha, and basic fibroblast growth factor, bFGF) which is ultimately responsible for the histological features including angiogenesis, epidermal keratinocyte hyperproliferation, and T cell infiltration. This study will bring into clear focus the cascade of molecular events that we currently postulate to be of major importance in AIDS-related psoriasis, which is: HIV -> T Cell -> lymphokines -> dermal dendrocyte -> IL-1, GM-CSF, TNF-alpha, bFGF -> psoriasis. Our experimental approach includes: identification of dermal dendrocytes in tissue sections with correlation to disease activity; isolation and characterization of dermal dendrocytes in vitro; examination of how dermal dendrocytes influence other indigenous cell types of the skin in both in-vitro and in-vivo experiments; characterization of the interaction between HIV and dermal dendrocytes. Techniques used in these experiments include: cell culture; differential centrifugation; immunohistochemical staining, in-vitro macrophage and lymphocyte functional studies; bioassays and Northern blot analysis animal studies and various molecular biological studies of the HIV virus/dermal dendrocyte interaction. We will examine the role of activated dermal dendrocytes in producing psoriasiform changes in rabbit skin. These model systems, together with descriptive in-vitro results, will substantially advance our understanding of the complex immunoregulatory dysfunction characteristic of AIDS-related skin diseases, such as psoriasis. Such new knowledge will lead to therapeutic strategies targeted at HIV activated dermal dendrocytes, and the consequent disordered cytokine network for the treatment of KS and psoriasis in AIDS patients.