Clinical studies of AIDS and the recognition of plasmacytoid dendritic cells (pDC)

Clinical observations in the natural history of acquired immunodeficiency syndrome (AIDS) and other immunodeficiencies have suggested a role for certain interferon (IFN)-producing cells (originally termed NIPC) in the host defense against opportunistic infection (OI). Identification of these cells with the previously described enigmatic cells resident in thymus and T cell areas of lymphoid tissues has led to improved understanding of mechanisms of induction of Th-1 immunity. The NIPC, now referred to as plasmacytoid pre-dendritic cells or plasmacytoid dendritic cells (pDC), may carry human immunodeficiency virus (HIV)-1 from the periphery into contact with immature T cells in lymphoid tissue, leading to infection of the T cells and selective ablation of the Th-l pathway. Progressive losses of pDC numbers and function during the course of HIV infection may eventually deprive the Th-1 pathway of essential IFN-α signaling, in turn needed for an interleukin-12 (IL-12) mediated IFN-γ response. Infection of the thymus by HIV-1 is both resisted, and later probably enhanced by IFN-α locally generated by HIV-stimulated and HIV-infected pDC. The resulting thymic pathology would then lead to failure of peripheral T cell repopulation. These pDC-related processes probably contribute to the pathogenesis of AIDS and explain the original clinical observations relating the IFN-production deficit to susceptibility to OI.