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

Replication and storage of virus are characteristic features of hyperplasti c lymphoid tissues in HIV infection. In opportunistic infections, HIV is sy nthesized by phagocytic mononuclear and Langhans'-type multinucleated macro phages that coexpress the dendritic cell-associated S-100 and p55 antigens. However, similar cells in hyperplastic tonsils and adenoids from HIV+ indi viduals were alternatively identified as macrophages or, on the basis of th e 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 reconc ile 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 specim ens (n = 11), the giant cells and their mononuclear counterpart were positi ve 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 macro phages. Furthermore, these cells were not unique to HIV+ specimens, being s een in 20% of hyperplastic T&A surgical specimens (n = 57) lacking HIV as w ell as in several types of granulomatous processes, such as sarcoidosis. Th ese cells appear to represent an activated phenotype that can develop indep endent of HIV, but that may represent a viral host in HIV-infected individu als. Thus, the giant and mononuclear cells that produce striking amounts of HIV in tonsils and adenoids are of macrophage origin, yet, as in opportuni stic infections, share dendritic cell-associated antigens, reflecting a com mon CD34(+) bone marrow progenitor.