Giant cell formation in Hodgkin's disease.

The identity of Reed-Sternberg cells in Hodgkin's disease has remained an unresolved issue, though many studies have addressed this question. Giant cells are usually formed either by endomitosis without cytoplasmic division or by cell fusion through cytokines or viruses. Growing evidence associates Epstein-Barr virus (EBV) with Hodgkin's disease, a major issue being whether EBV is a passenger virus or has an aetiological role. This communication describes experimental conditions enabling observation of giant cell cytogenesis from peripheral blood mononuclear cells in culture. Mononuclear cells were isolated from autologous peripheral blood and cocultured with a single-cell suspension obtained from Hodgkin's lymph nodes in a culture chamber where the two cell populations are isolated by a microporous membrane that allows only cytokines and viruses to pass through. Under these experimental conditions, giant cells are formed in the peripheral blood mononuclear cell fraction; some of them appear morphologically indistinguishable from Reed-Sternberg cells and their mononuclear variant, while others much resemble Langhans giant cells. Some of these giant cells are positive for EBV DNA by in situ hybridization. These results suggest that an EBV-dependent biological activity is responsible for giant cell cytogenesis originating from lymphocytes and monocytes, induced either by EBV and/or cytokines.