Th1-mediated Pathology in Mouse Models of Human Disease is Ameliorated by Concurrent Th2 Responses to Parasite Antigens
Epidemiologic evidence strongly suggests that improved standards of living are associated with an increased incidence of immune system-mediated disease. Allergy, autoimmunity, and within the focus of our laboratory, idiopathic inflammatory bowel disease, most notably Crohn's disease and ulcerative colitis, and progression of chronic gastritis to gastric cancer, are all mediated by proinflammatory immune responses induced by known or unknown antigens. A popular theory, known as the ‘hygiene hypothesis’ , suggests that improved health standards achieved through sanitation and vaccination, may in part be responsible for the apparent increase in immune system-mediated disease due to decreasing microbial and parasitic infections in humans, particularly in children. As antigenic exposure of children to infectious agents, especially parasites, has rapidly decreased, it is suspected that normally protective counter-regulatory Th2-type immune responses fail to develop, increasing the risk for aberrant pro-inflammatory responses in otherwise genetically pre-disposed individuals. This hypothesis has stimulated significant interest in development of animal models of Th1- and Th2-mediated disease to test this paradigm. This review illustrates some of the exciting evidence that Th1- mediated pathology in mouse models of helicobacter disease and diabetes is ameliorated by concurrent anti-inflammatory Th2 responses to parasite antigens and that initial application of these principles is benefiting human patients. The results from developing animal models of human disease not only support the hygiene hypothesis but also have led to novel therapies using parasite antigens to stimulate anti-inflammatory Th2-type responses to restore homeostasis in patients with aberrant Th1-type immune-mediated disease.
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Document Type: Review Article
Affiliations: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 16-825A, Cambridge, MA 02139, USA.
Publication date: February 1, 2004