We have attempted to delineate certain of the immunopathogenic mechanisms of human immunodeficiency virus (HIV) disease by studying the virologic and immunologic events associated with primary HIV infection. We previously demonstrated that extracellular virions are trapped in the follicular dendritic cell (FDC) network of the lymph nodes (LN) of HIV- infected patients during the clinically latent stage of disease when plasma viremia and virus expression are downregulated. In order to determine the temporal relationship between the decrease in plasma viremia, the downregulation of virus expression, and the trapping of virions in FDC, we studied acute primary infection in the simian immunodeficiency virus (SIV) model. Localization of SIV in the form of virus-infected cells in LN of monkeys is detected as early as 7 days post-inoculation. Trapping of virions in the FDC network is initially detected at 14 days and progressively increases over time, whereas the number of SIV-infected cells decrease. Trapping of virions is temporally associated with a rise in levels of complement-fixing antibodies. These studies indicate that the LN are the sites of establishment of SIV/HIV infection and that virus trapping in LN may be critical to the propagation of SIV/HIV disease. With regard to the immunological events associated with primary HIV infection, we studied six patients soon after primary HIV infection and into the early chronic stage of disease. We demonstrated major expansions in CD8+ T cells that belong to restricted sets of Vbeta families. These expansions coincided with the peak in viremia and decreased as virus was cleared. The vast majority of the expanded cell populations were activated and they mediated HIV-specific cytotoxicity. Nucleotide sequences of recombinant clones of the expanded Vas demonstrated the oligoclonal (antigen-specific) nature of these expansions. These expansions of CD8+ T cells expressing a particular Va family represent an important component of the primary immune response to HIV and should shed insight on the pathogenic mechanisms of HIV disease.
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