The macrophage origin of the HIV-expressing multinucleated giant cells in hyperplastic tonsils and adenoids

Replication and storage of virus are characteristic features of hyperplastic lymphoid tissues in HIV infection. In opportunistic infections, HIV is synthesized by phagocytic mononuclear and Langhans'-type multinucleated macrophages that coexpress the dendritic cell-associated S-100 and p55 antigens. However, similar cells in hyperplastic tonsils and adenoids from HIV+ individuals were alternatively identified as macrophages or, on the basis of the same S-100 and p55 staining, as dendritic cells. To consider establishing the role of these HIV-rich cells in HIV disease, it is important to reconcile this apparent discrepancy in identity. Hyperplastic tonsils and adenoid specimens were analyzed by HIV RNA in situ hybridization (ISH), light and transmission electron microscopy (TEM), and immunohistochemistry (IHC) (HIV Gag p24 protein, S-100, p55, CD68, HAM56, lysozyme, alpha-1-anti-trypsin, and alpha-1-anti-chymotrypsin). In HIV+ pediatric and adult surgical specimens (n = 11), the giant cells and their mononuclear counterpart were positive for both macrophage and p55 and S-100 IHC markers. In addition, TEM, p24 IHC, and ISH showed HIV expression by cells with typical features of macrophages. Furthermore, these cells were not unique to HIV+ specimens, being seen in 20% of hyperplastic T&A surgical specimens (n = 57) lacking HIV as well as in several types of granulomatous processes, such as sarcoidosis. These cells appear to represent an activated phenotype that can develop independent of HIV, but that may represent a viral host in HIV-infected individuals. Thus, the giant and mononuclear cells that produce striking amounts of HIV in tonsils and adenoids are of macrophage origin, yet, as in opportunistic infections, share dendritic cell-associated antigens, reflecting a common CD34+ bone marrow progenitor.