Section on Intercellular Interactions
Leonid Margolis, Section Head
The biology of any given cell depends upon a complex system of local contacts with cellular and non-cellular structures within the tissue. To understand the mechanism of cell behavior in vitro, it is necessary to develop a system to study these mechanisms in a native microenvironment of real tissue in vitro. This is particularly important in understanding the critical events in HIV-disease, which occurs inside the lymphoid tissue. Our goal is to develop such a system and to apply it in the study of HIV pathogenesis in human lymphoid tissue. We have developed histocultures of human tonsils that support the replication of various isolates of HIV-1, and demonstrate the hallmarks of HIV infection. This system was used to study the role of HIV-induced syncytia formation in HIV pathogenesis, as well as the relative contributions of host and viral factors to HIV disease. It was shown that the cell fusion occurring during syncytia formation may be an important pathogenic factor for HIV in human lymphoid tissue. The Unit continues to study cells in 3D cultures utilizing various techniques, including the NASA-designed Bioreactor.