Immunoglobulin E and effector cells in schistosomiasis.

Schistosomiasis is a chronic and debilitating disease, affecting 200 million people throughout the world. Infection by Schistosoma manson~ is characterized by the presence of adult worms m the portal and mesenteric veins of humans and other mammals, whereas S. haematobium worms live mostly in the urogenital venous system. A complex migratory cycle is initiated when infective larvae, shed by infected freshwater snails, penetrate the skin. The infective larvae transform into schistosomula in the host's skin and, over several weeks, develop into sexually mature, egglaying worms. The pathology in this disease occurs as a result of the parasite's eggs in the host tissues. Acquired resistance ro schistosome infection requires antibodydependent mechanisms. In all animal models and in humans, elevated immunoglobulin E (IgE) concentrations, including IgE specific for schistosomes, and blood and ussue eosinophilia are hallmarks of schistosomiasis. In mice, there is a functional dichotomy in the CD4 + T cell response to S. mansoni (1) -both T helper 1 (TH1) and TH2 responses are seen. Now it is thought that schistosome worms stimulate protective TH1 cell responses that are down-regulated by egg-induced TH2 cell responses. Like eosinophil and IgE levels, interleukin 4 (IL-4) and IL5 production by TH2 cells increase at about the time that the worms mature and egg production begins, suggesting a causal link between eggs and TH2 cell responses (2, 3). These results indicate that both expression of protective immunity and the pathological reactions are regulated by a complex network of coordinated responses, a T H cross-regulatory circuit (4). In rat, primate, and human schistosomiasis, antibody-dependent, cell-mediated cytotoxicity