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.

Type

Journal article

Journal

Immunity

Publication Date

10/1994

Volume

1

Pages

553 - 562

Keywords

Animals, Antibodies, Monoclonal, CD4-Positive T-Lymphocytes, Colitis, Colon, Inflammatory Bowel Diseases, Interferon-gamma, Interleukins, Leukocyte Common Antigens, Mice, Mice, Inbred BALB C, Mice, SCID, Models, Immunological, RNA, Messenger, T-Lymphocyte Subsets, Th1 Cells, Time Factors, Tumor Necrosis Factor-alpha