Department of Medicine, Allergy and Immunology Section, University of Pennsylvania, School of Medicine, Department of Parasitic Diseases, Division of Communicable Disease and Immunology, Walter Reed Army Institute of Research, Philadelphia, Pennsylvania 19104
These studies were designed to test the hypothesis that granulomatous hypersensitivity associated with schistosomiasis, its modulation, and subsequent morbidity are contingent on thymic-dependent lymphocyte function. Studies in athymic mice were integrated with in vitro studies on granuloma formation. Athymic animals tolerate low levels of infection well but are increasingly susceptible to morbidity as the challenge burden increases or becomes associated with simultaneous additional stress such as bacterial infection. In addition, the athymic animals produce smaller granulomas and fail to demonstrate accelerated granuloma formation, the spontaneous modulation of granulomas, or significant resistance to reinfection. These deficiencies could be reversed by thymic reconstitution. In vitro studies indicate that the response to egg antigens was due to the interaction of two subpopulations of T lymphocytes. Studies of “in vitro granuloma formation” augmented the in vivo findings, suggesting that the “in vitro granuloma” represents an excellent analog for delayed hypersensitivities; granuloma production was contingent on a macrophage function and a specific subpopulation of T lymphocytes defined as Ly1+. Granuloma modulation was due to two mechanisms, one contingent on direct suppression by Ly2,3+ cells and the other by feedback inhibition requiring Ly1,2,3+ cells. These studies suggest the feasibility of combined in vivo and in vitro technology to study the mechanisms of granuloma formation and subsequent morbidity.