Stein H, Spiegel H, Herbst H, Niedobitek G, Foss H D
Institut für Pathologie, Universitäts-Klinikum, Berlin-Steglitz.
Verh Dtsch Ges Pathol. 1991;75:4-19.
Currently discussed models of AIDS pathogenesis attribute a pivotal role to HIV-variants developing in T cells during the course of the disease resulting in an increasingly rapid depletion of the infected T cells. Such models do not however explain the morphological findings observed in AIDS lymphadenopathy. To clarify the significance of the hyperplasia and subsequent destruction of the lymphoid follicles in HIV-related lymphadenopathy, we used in situ hybridization in combination with immunohistological labelling techniques to identify the phenotype of HIV-infected cells in lymph nodes. In addition to few T helper cells, mainly in germinal centres, large amounts of HIV-RNA were found in CD4-negative follicular dendritic cells (FDC) rather than in macrophages or other cells. This finding is well in accordance with the recent observations made by other authors suggesting that purified FDC can be infected with HIV in vitro. Furthermore, TNF alpha expression is localized mainly in centroblasts (activated B cells) of germinal centres. TNF alpha, released by antigen-activated B cells in vitro, has been shown to induce HIV replication in latently infected T cells. On the basis of these observations we propose that latently infected CD4+ T cells, having entered germinal centres, start HIV replication under the influence of cytokines present in this microcompartment of all lymphoreticular tissues. Here the T cells infect FDC which, in turn, pass on the virus to new healthy T helper cells. This model may explain both peculiarities of the lymphadenopathy syndrome as well as the long latency period of HIV-infection, ultimately leading to AIDS.
目前所讨论的艾滋病发病机制模型认为，在疾病过程中T细胞内产生的HIV变异体起着关键作用，导致被感染的T细胞越来越快速地耗竭。然而，这类模型无法解释在艾滋病淋巴结病中所观察到的形态学表现。为了阐明HIV相关淋巴结病中淋巴滤泡增生及随后破坏的意义，我们运用原位杂交结合免疫组织学标记技术来识别淋巴结中被HIV感染细胞的表型。除了少数主要位于生发中心的辅助性T细胞外，在CD4阴性的滤泡树突状细胞（FDC）中发现了大量的HIV-RNA，而不是在巨噬细胞或其他细胞中。这一发现与其他作者最近的观察结果非常一致，这些观察结果表明纯化的FDC在体外可被HIV感染。此外，肿瘤坏死因子α（TNFα）的表达主要定位于生发中心的中心母细胞（活化的B细胞）。体外实验表明，抗原激活的B细胞释放的TNFα可诱导潜伏感染的T细胞中的HIV复制。基于这些观察结果，我们提出，进入生发中心的潜伏感染CD4+T细胞，在所有淋巴网状组织的这个微环境中存在的细胞因子的影响下开始HIV复制。在这里，T细胞感染FDC，而FDC又将病毒传递给新的健康辅助性T细胞。这个模型可以解释淋巴结病综合征的特点以及HIV感染的长潜伏期，最终导致艾滋病。
