[Lymphoid tissues and AIDS: role of lymphocytes and follicular dendritic cells (FDC)].

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.