title: Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells.
abstract: We have described a murine model of IBD that was induced in C.B-17 scid mice by transfer of the CD45RBhi subpopulation of CD4+ T cells from normal BALB/c mice and could be prevented by cotransfer of the CD45RBlo CD4+ T cell subset. Here we have dissected the mechanism of pathogenesis of IBD in this model and used this information for rational immunotherapy of the disease. CD4+ cells from diseased mice displayed a highly polarized Th1 pattern of cytokine synthesis upon polyclonal stimulation in vitro. The administration of anti-IFN gamma MAb to mice soon after T cell transfer prevented development of colitis for up to 12 weeks. Continual neutralization of TNF with anti-TNF MAbs reduced the incidence of severe disease; however, neutralization of TNF during only the first 3-4 weeks had no effect. Severe colitis was completely abrogated in mice treated systemically with rIL-10, but not with rIL-4.
authors.affiliation: DNAX Research Institute of Molecular and Cellular Biology Incorporated, Palo Alto, California 94040, USA.
authors.forename: F
authors.initials: F
authors.lastname: Powrie
authors.forename: M W
authors.initials: MW
authors.lastname: Leach
authors.forename: S
authors.initials: S
authors.lastname: Mauze
authors.forename: S
authors.initials: S
authors.lastname: Menon
authors.forename: L B
authors.initials: LB
authors.lastname: Caddle
authors.forename: R L
authors.initials: RL
authors.lastname: Coffman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D003092:Colitis / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D018448:Models, Immunological; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens