HLA-DR-positive dendritic cells of the normal human choroid plexus: a potential reservoir of HIV in the central nervous system

Abstract

In a previous study of choroid plexus (CPx) from patients with the acquired immunodeficiency syndrome (AIDS), we found a population of stromal cells infected with the human immunodeficiency virus (HIV). To determine whether these represented antigen-presenting dendritic cells, we examined the phenotype of normal human choroid plexus by light and electron microscopy (EM) and established the HIV-infected cell type by immunohistochemistry in AIDS cases with HIV-infected CPx. Monoclonal antibodies were used to detect class II major histocompatibility antigens (MHC), S-100 and S-100beta protein, lymphocytes, monocytes/macrophages, and HIV glycoprotein. A variable number of stromal cells had slightly elongated nuclei and long branching processes that were strongly immunoreactive for class II MHCs, rarely reactive for S-100 and S-100beta and immunonegative for monocyte/macrophage markers. Phagocytic activity was absent by EM and immunomarkers. They were numerous in the subepithelial region, and their processes occasionally extended toward the stromal capillaries or between the CPx epithelial cells. The HIV-infected cells were intensely immunoreactive for class II MHC markers and often displayed a dendritic morphology. These results document the presence of dendritic cells in the normal human CPx whose morphology and immunophenotype closely resemble those of DCs elsewhere in the body. They also show that these immunoreactive MHC class II cells are the cell type infected by HIV. We suggest that the functional activity of the CPx DCs is similar to that of antigen-presenting dendritic cells elsewhere in the body. This includes the potential to harbor HIV during the prolonged period of clinical latency, acting as a central nervous system reservoir of infection before the onset of AIDS.