Mucosal immunity and inflammation. II. The yin and yang of T cells in intestinal inflammation: pathogenic and protective roles in a mouse colitis model.
Inflammatory bowel disease (IBD) is a multifactorial immune disorder of uncertain etiology. The advent of several mouse models of mucosal inflammation that resemble IBD has provided insight into the mechanisms governing both normal and pathological mucosal immune function. In a widely used adoptive transfer model, the injection into immunodeficient mice of a subset of CD4(+) T lymphocytes, the CD4(+)CD45RBhigh cells, leads to inflammation of the intestine. Pathogenesis is due in part to the secretion of proinflammatory cytokines. The induction of colitis can be prevented by cotransfer of another CD4(+) subpopulation, the CD4(+)CD45RBlow T cells. This population behaves analogously to the CD4(+)CD45RBhigh population in terms of the acquisition of activation markers and homing to the host intestine. However, their lymphokine profile when activated is different, and anti-inflammatory cytokines secreted and/or induced by CD4(+)CD45RBlow T cells prevent colitis. In this themes article, a description of the adoptive transfer model is given, the factors that promote and prevent colitis pathogenesis are discussed, and some controversial aspects of the model are addressed.
De Winter
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Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Cheroutre
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Kronenberg
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D000818:Animals; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D016481:Helicobacter Infections; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D016207:Cytokines; D017493:Leukocyte Common Antigens