IMMUNOBIOLOGY OF SIV ASSOCIATED LYMPHOMAS

非霍奇金淋巴瘤(NHL)是一种与艾滋病相关的主要临床疾病 有问题。艾滋病相关非霍奇金淋巴瘤(AIDS-NHL)在组织学上具有异质性 和解剖分布，但特征是一组一致的 免疫生物学特征包括B细胞来源，单克隆性， 经常与EB病毒有关，细胞因子网络的放松管制，以及 原癌基因和抑癌基因中的特征性遗传损伤 基因。关于生物多样性基本机制的许多问题 这个系统中的淋巴增生症仍然没有答案，问题也是如此 关于临床干预的新方法，部分原因是 缺乏合适的动物模型。恒河猴感染 携带猴免疫缺陷病毒(SIV)的猕猴似乎代表着 一个很好的艾滋病模型-非霍奇金淋巴瘤。淋巴瘤发生在感染SIV的人中 恒河猴的发病率和动力学与 感染艾滋病毒的人群。发病率，解剖分布， 异质性和EBV样疱疹病毒(RhEBV)的存在 SIV相关淋巴瘤似乎模拟了临床情况 在感染艾滋病毒的艾滋病患者中观察到的情况相当准确。虽然 在猕猴中，淋巴瘤与SIV感染有关 在过去的十年里，人们对这种机制知之甚少。 病机在该系统中运行。当前的目标是 建议检查与SIV相关的关键方面 淋巴肿大以评估其对疾病的贡献 进程。首先，猴淋巴瘤将从形态上进行分类， 并对来源、克隆和特征的细胞类型进行评估 遗传损伤。第二，RhEBV感染在中国的意义 淋巴增生症将根据以下4个标准进行评估 与对照动物相比，淋巴瘤感染的发生 肿瘤细胞内的RhEBV，肿瘤相对于病毒的克隆性 感染，以及潜伏期相关和其他 淋巴瘤中的RhEBV基因。第三，将对假设进行评估 细胞因子失控通过以下途径在SIV相关淋巴肿瘤发生中起作用 刺激肿瘤细胞增殖，和/或通过改变 抗肿瘤免疫反应。这些可能性将通过以下方式进行评估 细胞因子及细胞因子受体表达模式的研究 淋巴瘤。从SIV感染时收集的血清中的细胞因子 对淋巴瘤的发展也将进行定义和量化。 这项拟议的研究将有助于理解 SIV相关淋巴肿大的作用机制 对于开发早期诊断的新方法至关重要， 治疗或预防。

Non-Hodgkin's lymphoma (NHL) is a major AIDS-related clinical problem. AIDS-associated NHL (AIDS-NHL) is heterogeneous in histology and anatomic distribution, but is characterized by a consistent set of immunobiologic features including B-cell origin, monoclonality, frequent association with EBV, deregulation of cytokine networks, and characteristic genetic lesions in proto-oncogenes and tumor suppressor genes. Many questions regarding the basic mechanisms of lymphomagenesis in this system remain unanswered, as do questions regarding novel approaches to clinical intervention, in part because of the lack of a suitable animal model. Infection of the rhesus macaque with simian immunodeficiency virus (SIV) appears to represent an excellent model for AIDS-NHL. Lymphoma occurs in the SIV-infected rhesus macaque with incidence and kinetics comparable to that in the HIV-infected population. The incidence, anatomical distribution, heterogeneity, and presence of an EBV-like herpesvirus (RhEBV) in SIV-associated lymphomas appears to model the clinical situation observed in HIV-infected AIDS patients quite accurately. Although lymphoma has been associated with SIV infection in the rhesus macaque for the past decade, little is known about the mechanisms of pathogenesis operative in that system. The objective of the present proposal is to examine critical aspects of SIV-associated lymphomagenesis in order to evaluate their contribution to the disease process. First, simian lymphomas will be classified morphologically, and evaluated for cell type of origin, clonality, and characteristic genetic lesions. Second, the significance of RhEBV infection in lymphomagenesis will be assessed based on 4 criteria incidence of infection in lymphomas as compared to control animals, occurrence of RhEBV within tumor cells, clonality of tumors with respect to viral infection, and patterns of expression of latency-associated and other RhEBV genes in lymphomas. Third, the hypothesis will be evaluated that cytokine deregulation acts in SIV-associated lymphomagenesis by stimulating tumor cell proliferation, and/or by altering the anti-tumor immune response. These possibilities will be evaluated by defining the patterns of cytokine and cytokine receptor expression in lymphomas. Cytokines in sera collected from the time of SIV-infection to the development of lymphoma will also be defined and quantified. The proposed study will contribute an understanding of the pathogenic mechanisms operative in SIV-associated lymphomagenesis that is essential to the development of new approaches to its early diagnosis, treatment or prevention.