Tacchetti C, Favre A, Moresco L, Meszaros P, Luzzi P, Truini M, Rizzo F, Grossi C E, Ciccone E
Department of Human Anatomy, University of Genova, Italy.
Am J Pathol. 1997 Feb;150(2):533-42.
To gain further insight into the pathogenesis of human immunodeficiency virus (HIV) infection, lymph nodes from seven asymptomatic HIV+ subjects were analyzed during the latent phase of disease. Both ultrastructural and immunohistochemical analyses revealed that, in all of the cases, plasma cells producing IgM/gamma were present in germinal centers. Secreted immunoglobulins formed extracellular deposits mimicking the follicular dendritic cell network. Immunoglobulin produced by germinal center plasma cells are specific for HIV because they bind the HIV env protein gp 120. Plasma cells producing antibodies with the same specificity were also abundant in the extrafollicular regions of lymph nodes. During the latent phase of infection, the virus largely accumulates within the germinal centers. Therefore, extracellular immunoglobulin may form immune complexes, as shown by the presence of HIV-specific antibodies, HIV particles, and complement components C3c, C3d, and C1q in the interdendritic spaces. When the ultrastructural localization of HIV in germinal centers was analyzed, abundant virus particles were found in the interdendritic spaces. In addition to this extracellular localization of HIV, receptor-mediated endocytosis of viral particles by follicular dendritic cells was observed. Complete HIV particles were found within the endosomal compartment of the follicular dendritic cells and, as complete viral particles, free in the cytoplasm, indicating that the virus may escape from the endocytic compartment. As the virus is abundant in the cytoplasm, this event leads to formation of a hidden reservoir within follicular dendritic cells. In this location, HIV escapes recognition by cytotoxic T lymphocytes. In contrast, virus budding indicating a productive infection of follicular dendritic cells that would render them susceptible to T-cell-mediated lysis has been seldom observed.
为了更深入了解人类免疫缺陷病毒（HIV）感染的发病机制，在疾病潜伏期对7名无症状HIV阳性受试者的淋巴结进行了分析。超微结构和免疫组织化学分析均显示，在所有病例中，生发中心均存在产生IgM/γ的浆细胞。分泌的免疫球蛋白形成模仿滤泡树突状细胞网络的细胞外沉积物。生发中心浆细胞产生的免疫球蛋白对HIV具有特异性，因为它们能结合HIV包膜蛋白gp 120。产生具有相同特异性抗体的浆细胞在淋巴结的滤泡外区域也很丰富。在感染潜伏期，病毒主要在生发中心内积聚。因此，细胞外免疫球蛋白可能形成免疫复合物，如在树突间隙中存在HIV特异性抗体、HIV颗粒以及补体成分C3c、C3d和C1q所示。当分析HIV在生发中心的超微结构定位时，在树突间隙中发现了大量病毒颗粒。除了HIV的这种细胞外定位外，还观察到滤泡树突状细胞对病毒颗粒的受体介导的内吞作用。在滤泡树突状细胞的内体区室中发现了完整的HIV颗粒，并且作为完整的病毒颗粒存在于细胞质中，这表明病毒可能从内吞区室中逃逸。由于病毒在细胞质中大量存在，这一事件导致在滤泡树突状细胞内形成一个隐藏的储存库。在这个位置，HIV逃避细胞毒性T淋巴细胞的识别。相反，很少观察到表明滤泡树突状细胞发生 productive 感染并使其易受T细胞介导的裂解的病毒出芽现象。
