Hodgkin's disease is a lymphoid malignancy characterized by the neoplastic Reed-Sternberg (RS) cell. Hodgkin's disease is also associated with impaired cellular immunity in both treated and untreated patients. The origin of RS cells and the basis for disordered cellular immunity are unknown. The human dendritic cell (DC), which represents a new class of leukocytes and is a potent stimulator of immune responses, is especially interesting in this regard. The DC is a plausible precursor of the RS cell, and alterations in DC function could contribute to altered cellular immunity in Hodgkin's disease. This project will better characterize RS cells and ascertain their possible relationship to DC. Surface markers of RS cells will be studied by tissue section staining using available leukocyte monoclonal antibodies, particularly to B cells and DC. Methods for enrichment of RS cells from Hodgkin's disease tissue will be developed which in turn should lead to better characterization of surface markers, evaluation of in vitro immune function, preparation of specific anti-RS cell monoclonal antibodies, and possible development of RS cell lines. Because RS cells are the pathologic hallmark of Hodgkin's disease, this work should provide a new focus on the etiology of this disease. If RS cells are related to DC, then Hodgkin's disease tissue would stimulate investigation of normal DC function and development of needed anti-DC monoclonal antibodies. Specific evaluation of DC in Hodgkin's disease might also clarify the disordered cellular immunity in this illness. Because of the DC's pivotal role in the stimulation of immune responses, this work is additionally important to transplantation immunology, particularly with regard to bone marrow transplantation in leukemia. The project is also pertinent to immunotherapy, insofar as the DC is a potent stimulator of the development of cytolytic T cells and other T cell functions.
